The presence of defects and detrimental reactions at NiO_(x)/perovskite interface extremely limit the efficiency performance and long-term stability of the perovskite solar cells(PSCs) based on NiO_(x).Herein,an amphi...The presence of defects and detrimental reactions at NiO_(x)/perovskite interface extremely limit the efficiency performance and long-term stability of the perovskite solar cells(PSCs) based on NiO_(x).Herein,an amphipathic molecule Triton X100(Triton) is modified on the NiO_(x)surface.The hydrophilic chain of Triton as a Lewis base additive can coordinate with the Ni3+on the NiO_(x)surface which can passivate the interfacial defects and hinder the detrimental reactions at the NiO_(x)/perovskite interface.Additionally,the hydrophobic chain of Triton protrudes from the NiO_(x)surface to prevent moisture from penetrating into the NiO_(x)/perovskite interface.Consequently,the NiO_(x)/Triton-based devices(MAPbI3as absorbing layer) show superior moisture and thermal stability,retaining 88.4% and 64.3% of the initial power conversion efficiency after storage in air(40%-50% relative humidity(RH)) at 25 ℃ for 1070 h and in N2at 85℃ for 800 h,respectively.Moreover,the efficiency increases from 17.59% to 19.89% because of the passivation defect and enhanced hole-extraction capability.Besides,the NiO_(x)/Triton-based PSCs with Cs_(0.05)(MA_(0.15)FA_(0.85))_(0.95)Pb(I_(0.85)Br_(0.15))3perovskite as the light-absorbing layer also exhibits better moisture and thermal stability compared to the control devices,indicating the viability of our strategies.Of particular note,a champion PCE of 22.35% and 20.46% was achieved for small-area(0.1 cm^(2)) and large-area(1.2 cm^(2)) NiO_(x)/Triton-based devices,respectively.展开更多
The main objective of the present study is to develop a selfmicellizing solid dispersion(SMSD)system of cyclosporine A(CsA)using an amphiphilic copolymer,poly[MPC-co-BMA](pMB)to improve the biopharmaceutical propertie...The main objective of the present study is to develop a selfmicellizing solid dispersion(SMSD)system of cyclosporine A(CsA)using an amphiphilic copolymer,poly[MPC-co-BMA](pMB)to improve the biopharmaceutical properties of CsA(Fig.1A).Unlike conventional carrier compounds,pMB would perform the bifunctional ability as both polymeric carrier of solid dispersion system and solubilizer derived from a high micellizing property,which could be considered beneficial for the production of highly water soluble formulation of poorly water soluble compound[1].Improvement in the aqueous solubility has been believed to be a key consideration for acquiring potent pharmacological effects of BCS class II drug like CsA.展开更多
Hydrophobic nanochannel plays a significant role in many physical, biological, and geological phenomena and ex- hibits impressive applications due to both its ubiquitous distribution and great ability to transport hyd...Hydrophobic nanochannel plays a significant role in many physical, biological, and geological phenomena and ex- hibits impressive applications due to both its ubiquitous distribution and great ability to transport hydrophobic molecules, including various oils and gases. Based on theoretical modeling, we herein reveal that the amphipathic Janus nanoparticles have a large probability to self-assemble into uninterrupted hydrophobic nanochannels inside the aqueous nano-space, al- though there are large portions of the Janus nanoparticles to be hydrophilic. The key to this observation is the attractions between the hydrophobic regimes on neighboring amphipathic Janus particles through hydrophobic interaction in aqueous nano-space. More surprisingly, the permeation efficiency of hydrophobic molecules through the uninterrupted hydrophobic channel in Janus particles aggregate is even higher than that in the aggregate of hydrophobic particles. We note that the proposed amphipathic Janus particles can be transported to the appropriate positions by the water since the hydrophilic regimes still remain a strong particle-water interaction. We also note that most natural subsurface rocks are not completely hydrophobic or hydrophilic but have complex surfaces with inhomogeneous wetting property. Our work therefore provides a detailed molecular level understanding of the formation of underground strata as well as the new insight for constructing the artificial hydrophobic channels for various applications, such as the design of proppants to enhance the recovery of the unconventional oil/gas.展开更多
Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the endocytosis.However,limited biological characterization methods restrict the study...Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the endocytosis.However,limited biological characterization methods restrict the study of the state of nanoparticles with different amphiphilicities on cell membranes.The understanding of interaction of amphiphilic particle with cell membrane is still lacking.Herein,by combining the dissipative particle dynamics(DPD)with the framework construction of mesoporous silica nanoparticles(MSNs),we demonstrate the enhanced endocytosis induced by the hydrophobicity.DPD results confirm that the presence of hydrophobic groups on the surface of nanoparticles can disturb the integrity of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)membrane and induce activation of phospholipids to a higher energy level,thereby facilitating the wrapping of nanoparticles.To validate the simulation findings,uniform MSNs with hydrophilic pure silica framework and two types of amphiphilic MSNs with varying hydrophilic organic groups in the framework are rationally synthesized by using different silane precursors.The obtained three kinds of MSNs show similar diameter(~100 nm)and mesopores(~2 nm),but distinct hydrophobicity/hydrophilicity ratio.The phenyl-bridged MSN with a carbon content of 27.1%exhibits enhanced cellular uptake,consistent with the theoretical simulation results.This work sheds light on how the surface amphipathicity influences endocytosis through the interaction with cell membrane.展开更多
Over the past few decades, cell penetrating peptides （CPPs） have become an important class of drug carders for small molecules, proteins, genes and nanoparticle systems. CPPs represent a very diverse set of short pe...Over the past few decades, cell penetrating peptides （CPPs） have become an important class of drug carders for small molecules, proteins, genes and nanoparticle systems. CPPs represent a very diverse set of short peptide sequences （10-30 amino acids）, generally classified as cationic or amphipathic, with various mechanisms in cellular internalization. In this review, a more comprehensive assessment of the chemical structural characteristics, including net cationic charge, hydrophobicity and helicity was assembled for a large set of commonly used CPPs, and compared to results from numerous in vivo drug delivery studies. This detailed information can aid in the design and selection of effective CPPs for use as transport carriers in the delivery of different types of drug for therapeutic applications.展开更多
Rechargeable aqueous zinc-ion batteries are expected to be widely deployed for grind-scale energy storage due to the merits of low expenditure,safety,and so on.However,challenges on the Zn anode,including dendrite gro...Rechargeable aqueous zinc-ion batteries are expected to be widely deployed for grind-scale energy storage due to the merits of low expenditure,safety,and so on.However,challenges on the Zn anode,including dendrite growth and parasitic reactions with aqueous electrolytes hinder its advancement.Hereby,an amphipathic ionic sieve(AIS)membrane was designed to screen Zn^(2+)from the bulk of aqueous electrolyte by ruling out water solvent and assisting Zn^(2+)to deposit with a smooth morphology under a confined shielding.These benign characteristics enabled AIS to run Zn symmetric cells over 2300 h with a voltage of 1 mA h·cm^(−2) at each cycle and tolerated long-term standby for more than 3 months.A low self-discharge rate and outstanding cycling stability were realized in V_(2)O_(5)/Zn batteries at equal weight for cathode and anode(N/P ratio≈1.39).This asymmetrical wetting separator proved a facile strategy to solve interfacial dendrites and parasitic reactions in Zn metal-based batteries.展开更多
It has been attempted to immobilize organic mono layer on semiconductor surface as functional materials. Silicon surface was especially noticed to develop highly efficient and functional devices, and the silicon devic...It has been attempted to immobilize organic mono layer on semiconductor surface as functional materials. Silicon surface was especially noticed to develop highly efficient and functional devices, and the silicon devices were expected for the immobilized surface with organic layer. Then we have attempted the immobilization by the mono layer on the hydrogen terminated silicon surface with the alkyl base indicated hydrophobic by using a surfactant. We have observed interactions of immobilized molecules and organic molecules adsorbed on hydrogen terminated Si(111), which is aerosol OT as known surfactant and 4-cyanophenol as shown amphipathic molecule. The aerosol OT inhibited oxidation of Si(111) surface by adsorption to the hydrogen terminated surface to indicate hydrophobic. The 4-cyanophenol made the surface oxide by adsorption, and was desorbed by forming hydrophilic Si surface. In the case of the mixed solution by the aerosol OT and 4-cyanophenol, the aerosol OT controlled the surface oxidation on the hydrogen terminated Si against the 4-cyanophenol.展开更多
Infection in hard tissue regeneration is a clinically-relevant challenge.Development of scaffolds with dual function for promoting bone/dental tissue growth and preventing bacterial infections is a critical need in th...Infection in hard tissue regeneration is a clinically-relevant challenge.Development of scaffolds with dual function for promoting bone/dental tissue growth and preventing bacterial infections is a critical need in the field.Here we fabricated hybrid scaffolds by intrafibrillar-mineralization of collagen using a biomimetic process and subsequently coating the scaffold with an antimicrobial designer peptide with cationic and amphipathic properties.The highly hydrophilic mineralized collagen scaffolds provided an ideal substrate to form a dense and stable coating of the antimicrobial peptides.The amount of hydroxyapatite in the mineralized fibers modulated the rheological behavior of the scaffolds with no influence on the amount of recruited peptides and the resulting increase in hydrophobicity.The developed scaffolds were potent by contact killing of Gram-negative Escherichia coli and Gram-positive Streptococcus gordonii as well as cytocompatible to human bone marrow-derived mesenchymal stromal cells.The process of scaffold fabrication is versatile and can be used to control mineral load and/or intrafibrillar-mineralized scaffolds made of other biopolymers.展开更多
Three-way junctions are characteristic structures of the tubular endoplasmic reticulum (ER) network. Junctions are formed through atlastin (ATL)-mediated membrane fusion and stabilized by lunapark (Lnp). However, how ...Three-way junctions are characteristic structures of the tubular endoplasmic reticulum (ER) network. Junctions are formed through atlastin (ATL)-mediated membrane fusion and stabilized by lunapark (Lnp). However, how Lnp is preferentially enriched at three-way junctions remains elusiveHere, we showed that Lnp loses its junction localization when ATLs are deleted. Reintroduction of ATL1 R77A and ATL3, which have been shown to cluster at the junctions, but not wild-type ATL1, relocates Lnp to the junctions. Mutations in the Nmyristoylation site or hydrophobic residues in the coiled coil (CC1) of Lnp N-terminus (NT) cause mis-targeting of LnpConversely, deletion of the lunapark motif in the C-terminal zinc fin ger domain, which affects the homooligomerization of Lnp, does not alter its localizationPurified Lnp-NT attaches to the membrane in a myristoylation- dependent manner. The mutation of hydrophobic residues in CC1 does not affect membrane association, but compromises ATL interactionsIn addition, Lnp-NT inhibits ATL-mediated vesicle fusion in vitro. These results suggest that CC1 in Lnp-NT contacts junction-enriched ATLs for proper localization;subsequently, further ATL activity is limited by Lnp after the junction is formed. The proposed mechanism ensures coordinated actions of ATL and Lnp in generating and maintaining three-way junctions.展开更多
Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin aV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We...Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin aV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin aV and SIN3B expressions in HCC patients and tumor cell lines with different metastatic potentials. Overexpression of SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed when integrin αV expression was silenced. Interestingly, SIN3B stimulated integrin aV subunit promoter activity only in the presence of sulfatide. Importantly, SIN3B was identified in the complex with sulfatide by mass spectrometry. Fat blot assay indicated that SIN3B specifically interacted with sulfatide. Molecular modeling suggested that sulfatide induced the conformational change of SIN3B from compacted α-helices to a relaxed β-sheet in PAH2 domain. The data of immunoprecipitation and ChIP assay indicated that altered SIN3B lost the binding affinity with MAD1 and HDAC2, which reduced the recruitment of HDAC2 on integrin aV gene promoter and prevented the deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B promoted the transcriptional activation of the integrin αV subunit gene promoter by reducing interaction with HDAC2.展开更多
基金supported by the National Key Research and Development Program of China(2018YFA0208701)the National Natural Science Foundation of China(21773308)+7 种基金the Research Funds of Renmin University of China(2017030013,201903020 and 20XNH059)the Fundamental Research Funds for Central Universities(China)supported by the Solar Energy Research Institute of Singapore(SERIS) at the National University of Singapore(NUS)supported by NUSthe National Research Foundation Singapore(NRF)the Energy Market Authority of Singapore(EMA)the Singapore Economic Development Board(EDB)the financial support from the China Scholarship Council(CSC) funding。
文摘The presence of defects and detrimental reactions at NiO_(x)/perovskite interface extremely limit the efficiency performance and long-term stability of the perovskite solar cells(PSCs) based on NiO_(x).Herein,an amphipathic molecule Triton X100(Triton) is modified on the NiO_(x)surface.The hydrophilic chain of Triton as a Lewis base additive can coordinate with the Ni3+on the NiO_(x)surface which can passivate the interfacial defects and hinder the detrimental reactions at the NiO_(x)/perovskite interface.Additionally,the hydrophobic chain of Triton protrudes from the NiO_(x)surface to prevent moisture from penetrating into the NiO_(x)/perovskite interface.Consequently,the NiO_(x)/Triton-based devices(MAPbI3as absorbing layer) show superior moisture and thermal stability,retaining 88.4% and 64.3% of the initial power conversion efficiency after storage in air(40%-50% relative humidity(RH)) at 25 ℃ for 1070 h and in N2at 85℃ for 800 h,respectively.Moreover,the efficiency increases from 17.59% to 19.89% because of the passivation defect and enhanced hole-extraction capability.Besides,the NiO_(x)/Triton-based PSCs with Cs_(0.05)(MA_(0.15)FA_(0.85))_(0.95)Pb(I_(0.85)Br_(0.15))3perovskite as the light-absorbing layer also exhibits better moisture and thermal stability compared to the control devices,indicating the viability of our strategies.Of particular note,a champion PCE of 22.35% and 20.46% was achieved for small-area(0.1 cm^(2)) and large-area(1.2 cm^(2)) NiO_(x)/Triton-based devices,respectively.
文摘The main objective of the present study is to develop a selfmicellizing solid dispersion(SMSD)system of cyclosporine A(CsA)using an amphiphilic copolymer,poly[MPC-co-BMA](pMB)to improve the biopharmaceutical properties of CsA(Fig.1A).Unlike conventional carrier compounds,pMB would perform the bifunctional ability as both polymeric carrier of solid dispersion system and solubilizer derived from a high micellizing property,which could be considered beneficial for the production of highly water soluble formulation of poorly water soluble compound[1].Improvement in the aqueous solubility has been believed to be a key consideration for acquiring potent pharmacological effects of BCS class II drug like CsA.
基金Project supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB10040304)the National Natural Science Foundation of China(Grant Nos.51490654,11290164,and U1262109)the Key Research Program of Chinese Academy of Sciences(Grant No.KJZDEW-M03)
文摘Hydrophobic nanochannel plays a significant role in many physical, biological, and geological phenomena and ex- hibits impressive applications due to both its ubiquitous distribution and great ability to transport hydrophobic molecules, including various oils and gases. Based on theoretical modeling, we herein reveal that the amphipathic Janus nanoparticles have a large probability to self-assemble into uninterrupted hydrophobic nanochannels inside the aqueous nano-space, al- though there are large portions of the Janus nanoparticles to be hydrophilic. The key to this observation is the attractions between the hydrophobic regimes on neighboring amphipathic Janus particles through hydrophobic interaction in aqueous nano-space. More surprisingly, the permeation efficiency of hydrophobic molecules through the uninterrupted hydrophobic channel in Janus particles aggregate is even higher than that in the aggregate of hydrophobic particles. We note that the proposed amphipathic Janus particles can be transported to the appropriate positions by the water since the hydrophilic regimes still remain a strong particle-water interaction. We also note that most natural subsurface rocks are not completely hydrophobic or hydrophilic but have complex surfaces with inhomogeneous wetting property. Our work therefore provides a detailed molecular level understanding of the formation of underground strata as well as the new insight for constructing the artificial hydrophobic channels for various applications, such as the design of proppants to enhance the recovery of the unconventional oil/gas.
基金supported by the National Natural Science Foundation of China(Nos.22075049,22305042,22305041,21875043,22088101,21905052,and 51961145403)the National Key R&D Program of China(No.2018YFA0209401)+4 种基金the Key Basic Research Program of Science and Technology Commission of Shanghai Municipality(No.22JC1410200)the Natural Science Foundation of Shanghai(Nos.22ZR1478900 and 20490710600)the Shanghai Science and Technology Innovation Action Plan Morning Star Project(Sail Special,Nos.20QA1401200,22YF1402200,and 23YF1401900)the Shanghai Pilot Program for Basic Research-Fudan University(No.22TQ004)the Fundamental Research Funds for the Central Universities(No.20720220010).
文摘Due to the amphiphilic nature of phospholipids in the cell membrane,the amphipathicity of the nanomedicine plays a crucial role in the endocytosis.However,limited biological characterization methods restrict the study of the state of nanoparticles with different amphiphilicities on cell membranes.The understanding of interaction of amphiphilic particle with cell membrane is still lacking.Herein,by combining the dissipative particle dynamics(DPD)with the framework construction of mesoporous silica nanoparticles(MSNs),we demonstrate the enhanced endocytosis induced by the hydrophobicity.DPD results confirm that the presence of hydrophobic groups on the surface of nanoparticles can disturb the integrity of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)membrane and induce activation of phospholipids to a higher energy level,thereby facilitating the wrapping of nanoparticles.To validate the simulation findings,uniform MSNs with hydrophilic pure silica framework and two types of amphiphilic MSNs with varying hydrophilic organic groups in the framework are rationally synthesized by using different silane precursors.The obtained three kinds of MSNs show similar diameter(~100 nm)and mesopores(~2 nm),but distinct hydrophobicity/hydrophilicity ratio.The phenyl-bridged MSN with a carbon content of 27.1%exhibits enhanced cellular uptake,consistent with the theoretical simulation results.This work sheds light on how the surface amphipathicity influences endocytosis through the interaction with cell membrane.
文摘Over the past few decades, cell penetrating peptides （CPPs） have become an important class of drug carders for small molecules, proteins, genes and nanoparticle systems. CPPs represent a very diverse set of short peptide sequences （10-30 amino acids）, generally classified as cationic or amphipathic, with various mechanisms in cellular internalization. In this review, a more comprehensive assessment of the chemical structural characteristics, including net cationic charge, hydrophobicity and helicity was assembled for a large set of commonly used CPPs, and compared to results from numerous in vivo drug delivery studies. This detailed information can aid in the design and selection of effective CPPs for use as transport carriers in the delivery of different types of drug for therapeutic applications.
基金supported by the National Natural Science Foundation of China(grant no.51803054)the Science and Technology Innovation Program of Hunan Province,China(grant no.2023RC3154)+2 种基金the Natural Science Foundation of Hunan Province(grant no.2020JJ3022)the scientific research projects of Education Department of Hunan Province(grant nos.23A0188 and 23B0221)the Natural Sciences and Engineering Research Council of Canada,University of Waterloo and Waterloo Institute for Nanotechnology,Canada.
文摘Rechargeable aqueous zinc-ion batteries are expected to be widely deployed for grind-scale energy storage due to the merits of low expenditure,safety,and so on.However,challenges on the Zn anode,including dendrite growth and parasitic reactions with aqueous electrolytes hinder its advancement.Hereby,an amphipathic ionic sieve(AIS)membrane was designed to screen Zn^(2+)from the bulk of aqueous electrolyte by ruling out water solvent and assisting Zn^(2+)to deposit with a smooth morphology under a confined shielding.These benign characteristics enabled AIS to run Zn symmetric cells over 2300 h with a voltage of 1 mA h·cm^(−2) at each cycle and tolerated long-term standby for more than 3 months.A low self-discharge rate and outstanding cycling stability were realized in V_(2)O_(5)/Zn batteries at equal weight for cathode and anode(N/P ratio≈1.39).This asymmetrical wetting separator proved a facile strategy to solve interfacial dendrites and parasitic reactions in Zn metal-based batteries.
文摘It has been attempted to immobilize organic mono layer on semiconductor surface as functional materials. Silicon surface was especially noticed to develop highly efficient and functional devices, and the silicon devices were expected for the immobilized surface with organic layer. Then we have attempted the immobilization by the mono layer on the hydrogen terminated silicon surface with the alkyl base indicated hydrophobic by using a surfactant. We have observed interactions of immobilized molecules and organic molecules adsorbed on hydrogen terminated Si(111), which is aerosol OT as known surfactant and 4-cyanophenol as shown amphipathic molecule. The aerosol OT inhibited oxidation of Si(111) surface by adsorption to the hydrogen terminated surface to indicate hydrophobic. The 4-cyanophenol made the surface oxide by adsorption, and was desorbed by forming hydrophilic Si surface. In the case of the mixed solution by the aerosol OT and 4-cyanophenol, the aerosol OT controlled the surface oxidation on the hydrogen terminated Si against the 4-cyanophenol.
基金Professor Jakub Tolar from the University of Minnesota for donating S.gordonii,E.coli,and hBM-MSCs,respectively.The authors also acknowledge Neus BahíVives from Eurecat for technical assistance with the TGA/DTG analysis.This research was supported by the National Institute for Dental and Craniofacial Research of the National Institutes of Health[grant number R01DE026117 to C.A.,T90DE0227232 to N.G.F.],the National Institutes of Health’s National Center for Advancing Translational Sciences[Translational Research Development Program-TRDP award to Z.Y.from grant UL1TR002494],the Fundamental Research Funds for the Central Universities[grant number 2042020kf0191 to X.Z.],the National Natural Science Foundation of China[grant number 81400506 to Y.Q.]and the Natural Science Foundation of Guangdong Province[grant number 2018B030311040 to Y.Q.].NGF acknowledges support from a 3 M Science and Technology Fellowship.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Parts of this work were carried out in the University of Minnesota I.T.Characterization Facility,which receives partial support from NSF through the MRSEC program.Confocal laser scanning microscopy was performed at the University of Minnesota-University Imaging Center.
文摘Infection in hard tissue regeneration is a clinically-relevant challenge.Development of scaffolds with dual function for promoting bone/dental tissue growth and preventing bacterial infections is a critical need in the field.Here we fabricated hybrid scaffolds by intrafibrillar-mineralization of collagen using a biomimetic process and subsequently coating the scaffold with an antimicrobial designer peptide with cationic and amphipathic properties.The highly hydrophilic mineralized collagen scaffolds provided an ideal substrate to form a dense and stable coating of the antimicrobial peptides.The amount of hydroxyapatite in the mineralized fibers modulated the rheological behavior of the scaffolds with no influence on the amount of recruited peptides and the resulting increase in hydrophobicity.The developed scaffolds were potent by contact killing of Gram-negative Escherichia coli and Gram-positive Streptococcus gordonii as well as cytocompatible to human bone marrow-derived mesenchymal stromal cells.The process of scaffold fabrication is versatile and can be used to control mineral load and/or intrafibrillar-mineralized scaffolds made of other biopolymers.
基金National Key Research and Development Program (Grant No. 2016YFA0500201)the National Natural Science Foundation of China (Grant Nos. 31225006 and 3142100024).
文摘Three-way junctions are characteristic structures of the tubular endoplasmic reticulum (ER) network. Junctions are formed through atlastin (ATL)-mediated membrane fusion and stabilized by lunapark (Lnp). However, how Lnp is preferentially enriched at three-way junctions remains elusiveHere, we showed that Lnp loses its junction localization when ATLs are deleted. Reintroduction of ATL1 R77A and ATL3, which have been shown to cluster at the junctions, but not wild-type ATL1, relocates Lnp to the junctions. Mutations in the Nmyristoylation site or hydrophobic residues in the coiled coil (CC1) of Lnp N-terminus (NT) cause mis-targeting of LnpConversely, deletion of the lunapark motif in the C-terminal zinc fin ger domain, which affects the homooligomerization of Lnp, does not alter its localizationPurified Lnp-NT attaches to the membrane in a myristoylation- dependent manner. The mutation of hydrophobic residues in CC1 does not affect membrane association, but compromises ATL interactionsIn addition, Lnp-NT inhibits ATL-mediated vesicle fusion in vitro. These results suggest that CC1 in Lnp-NT contacts junction-enriched ATLs for proper localization;subsequently, further ATL activity is limited by Lnp after the junction is formed. The proposed mechanism ensures coordinated actions of ATL and Lnp in generating and maintaining three-way junctions.
文摘Paired amphipathic helix protein (SIN3B) is a transcription corepressor for many genes. Here we show a different regulation mechanism of integrin aV gene expression by SIN3B in human hepatocellular carcinoma (HCC). We first observed a close relationship between Integrin aV and SIN3B expressions in HCC patients and tumor cell lines with different metastatic potentials. Overexpression of SIN3B significantly accelerated the cell migration rate of SMMC-7721, but failed when integrin αV expression was silenced. Interestingly, SIN3B stimulated integrin aV subunit promoter activity only in the presence of sulfatide. Importantly, SIN3B was identified in the complex with sulfatide by mass spectrometry. Fat blot assay indicated that SIN3B specifically interacted with sulfatide. Molecular modeling suggested that sulfatide induced the conformational change of SIN3B from compacted α-helices to a relaxed β-sheet in PAH2 domain. The data of immunoprecipitation and ChIP assay indicated that altered SIN3B lost the binding affinity with MAD1 and HDAC2, which reduced the recruitment of HDAC2 on integrin aV gene promoter and prevented the deacetylation of the histone 3. In conclusion, this study demonstrated that SIN3B promoted the transcriptional activation of the integrin αV subunit gene promoter by reducing interaction with HDAC2.
