电压门控离子通道结构生物学研究进展
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摘要
离子通道介导离子的跨膜运转,在生物体内的物质交换、能量传递和信号传导过程中发挥关键作用。近年来,离子通道结构生物学研究极大地推动了人们对离子通道的离子选择性和门控机制的认识。电压门控钾通道结构生物学研究阐明了钾离子选择性的结构基础和电压门控机制;电压门控钠通道结构生物学研究揭示了钠通道的慢失活和快失活机制;瞬时受体电位通道结构生物学研究提供了瞬时受体电位通道复杂多样的结构和配体门控机制。本文总结了近年来离子通道结构生物学的研究进展,并展望了未来离子通道结构生物学的发展。
Ion channels mediate ion transport across membranes, and play vital roles in processes of matter exchange, energy transfer and signal transduction in living organisms. Recently, structural studies of ion channels have greatly advanced our understanding of their ion selectivity and gating mechanisms. Structural studies of voltage-gated potassium channels elucidate the structural basis for potassium selectivity and voltage-gating mechanism; structural studies of voltage-gated sodium channels reveal their slow and fast inactivation mechanisms; and structural studies of transient receptor potential(TRP) channels provide complex and diverse structures of TRP channels, and their ligand gating mechanisms. In the article we summarize recent progress on ion channel structural biology, and outlook the prospect of ion channel structural biology in the future.
Ion channels mediate ion transport across membranes, and play vital roles in processes of matter exchange, energy transfer and signal transduction in living organisms. Recently, structural studies of ion channels have greatly advanced our understanding of their ion selectivity and gating mechanisms. Structural studies of voltage-gated potassium channels elucidate the structural basis for potassium selectivity and voltage-gating mechanism; structural studies of voltage-gated sodium channels reveal their slow and fast inactivation mechanisms; and structural studies of transient receptor potential(TRP) channels provide complex and diverse structures of TRP channels, and their ligand gating mechanisms. In the article we summarize recent progress on ion channel structural biology, and outlook the prospect of ion channel structural biology in the future.
引文
[1]DOYLE D A,MORAIS C J,PFUETZNER R A,et al.The structure of the potassium channel:molecular basis of K+conduction and selectivity[J].Science,1998,280(5360):69-77.
[2]YU F H,CATTERALL W A.The VGL-chanome:a protein superfamily specialized for electrical signaling and ionic homeostasis[J].Sci STKE,2004,2004(253):re15.
[3]JIANG Y,LEE A,CHEN J,et al.X-ray structure of a voltage-dependent K+channel[J].Nature,2003,423(6935):33-41.
[4]LONG S B,CAMPBELL E B,MACKINNON R.Crystal structure of a mammalian voltage-dependent shaker family K+channel[J].Science,2005,309(5736):897-903.
[5]LONG S B,CAMPBELL E B,MACKINNON R.Voltage sensor of Kv1.2:structural basis of electromechanical coupling[J].Science,2005,309(5736):903-908.
[6]LONG S B,TAO X,CAMPBELL E B,et al.Atomic structure of a voltage-dependent K+channel in a lipid membrane-like environment[J].Nature,2007,450(7168):376-382.
[7]WHICHER J R,MACKINNON R.Structure of the voltage-gated K+channel Eag1 reveals an alternative voltage sensing mechanism[J].Science,2016,353(6300):664-669.
[8]TAO X,HITE R K,MACKINNON R.Cryo-EMstructure of the open high-conductance Ca2+-activated K+channel[J].Nature,2017,541(7635):46-51.
[9]HITE R K,TAO X,MACKINNON R.Structural basis for gating the high-conductance Ca2+-activated K+channel[J].Nature,2017,541(7635):52-57.
[10]WANG W,MACKINNON R.Cryo-EM structure of the open human ether-à-go-go-related K+channel hERG[J].Cell,2017,169(3):422-430.e10.
[11]SUN J,MACKINNON R.Cryo-EM structure of a KCNQ1/CaM complex reveals insights into congenital long QT syndrome[J].Cell,2017,169(6):1042-1050.e9.
[12]ZHOU Y,MORAIS-CABRAL J H,KAUFMAN A,et al.Chemistry of ion coordination and hydration revealed by a K+channel-Fab complex at 2.0?resolution[J].Nature,2001,414(6859):43-48.
[13]YE S,LI Y,JIANG Y.Novel insights into K+selectivity from high-resolution structures of an open K+channel pore[J].Nat Struct Mol Biol,2010,17(8):1019-1023.
[14]SAUER D B,ZENG W,CANTY J,et al.Sodium and potassium competition in potassium-selective and nonselective channels[J].Nat Commun,2013,4:2721.
[15]TAO X,LEE A,LIMAPICHAT W,et al.A gating charge transfer center in voltage sensors[J].Science,2010,328(5974):67-73.
[16]TAKESHITA K,SAKATA S,YAMASHITA E,et al.X-ray crystal structure of voltage-gated proton channel[J].Nat Struct Mol Biol,2014,21(4):352-357.
[17]GUO J,ZENG W,CHEN Q,et al.Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana[J].Nature,2016,531(7593):196-201.
[18]PAYANDEH J,SCHEUER T,ZHENG N,et al.The crystal structure of a voltage-gated sodium channel[J].Nature,2011,475(7356):353-358.
[19]ZHANG X,REN W,DECAEN P,et al.Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel[J].Nature,2012,486(7401):130-134.
[20]PAYANDEH J,GAMAL E T M,SCHEUER T,et al.Crystal structure of a voltage-gated sodium channel in two potentially inactivated states[J].Nature,2012,486(7401):135-139.
[21]SULA A,BOOKER J,NG L C T,et al.The complete structure of an activated open sodium channel[J].Nat Commun,2017,8:14205.
[22]AHUJA S,MUKUND S,DENG L,et al.Structural basis of Nav1.7 inhibition by an isoform-selective smallmolecule antagonist[J].Science,2015,350(6267):aac5464.
[23]SHEN H,ZHOU Q,PAN X,et al.Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution[J].Science,2017,355(6328):eaal4326.
[24]SHEN H,LI Z,JIANG Y,et al.Structural basis for the modulation of voltage-gated sodium channels by animal toxins[J].Science,2018,362(6412):eaau2596.
[25]YAN Z,ZHOU Q,WANG L,et al.Structure of the Nav1.4-β1 complex from electric eel[J].Cell,2017,170(3):470-482.e11.
[26]PAN X,LI Z,ZHOU Q,et al.Structure of the human voltage-gated sodium channel Nav1.4 in complex withβ1[J].Science,2018,362(6412):eaau2486.
[27]NAYLOR C E,BAGNéRIS C,DECAEN P G,et al.Molecular basis of ion permeability in a voltage-gated sodium channel[J].EMBO J,2016,35(8):820-830.
[28]CLAPHAM D E,RUNNELS L W,STRüBING C.The TRP ion channel family[J].Nat Rev Neurosci,2001,2(6):387-396.
[29]CAO E,LIAO M,CHENG Y,et al.TRPV1 structures in distinct conformations reveal activation mechanisms[J].Nature,2013,504(7478):113-118.
[30]LIAO M,CAO E,JULIUS D,et al.Structure of the TRPV1 ion channel determined by electron cryomicroscopy[J].Nature,2013,504(7478):107-112.
[31]GAO Y,CAO E,JULIUS D,et al.TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action[J].Nature,2016,534(7607):347-351.
[32]PAULSEN C E,ARMACHE J P,GAO Y,et al.Structure of the TRPA1 ion channel suggests regulatory mechanisms[J].Nature,2015,525(7570):552.
[33]ZUBCEVIC L,HERZIK M A JR,CHUNG B C,et al.Cryo-electron microscopy structure of the TRPV2 ion channel[J].Nat Struct Mol Biol,2016,23(2):180-186.
[34]HUYNH K W,COHEN M R,JIANG J,et al.Structure of the full-length TRPV2 channel by cryo-EM[J].Nat Commun,2016,7:11130.
[35]ZUBCEVIC L,LE S,YANG H,et al.Conformational plasticity in the selectivity filter of the TRPV2 ion channel[J].Nat Struct Mol Biol,2018,25(5):405-415.
[36]DENG Z,PAKNEJAD N,MAKSAEV G,et al.CryoEM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms[J].Nat Struct Mol Biol,2018,25(3):252-260.
[37]TET H,LODOWSKI D T,HUYNH K W,et al.Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM[J].Nat Struct Mol Biol,2018,25(1):53-60.
[38]SAOTOME K,SINGH A K,YELSHANSKAYA M V,et al.Crystal structure of the epithelial calcium channel TRPV6[J].Nature,2016,534(7608):506-511.
[39]MCGOLDRICK L L,SINGH A K,SAOTOME K,et al.Opening of the human epithelial calcium channel TRPV6[J].Nature,2018,553(7687):233-237.
[40]SHEN P S,YANG X,DECAEN P G,et al.The structure of the polycystic kidney disease channel PKD2 in lipid nanodiscs[J].Cell,2016,167(3):763-773.e11.
[41]GRIEBEN M,PIKE A C W,SHINTRE C A,et al.Structure of the polycystic kidney disease TRP channel polycystin-2(PC2)[J].Nat Struct Mol Biol,2017,24(2):114-122.
[42]WILKES M,MADEJ M G,KREUTER L,et al.Molecular insights into lipid-assisted Ca2+regulation of the TRP channel polycystin-2[J].Nat Struct Mol Biol,2017,24(2):123-130.
[43]SCHMIEGE P,FINE M,BLOBEL G,et al.Human TRPML1 channel structures in open and closed conformations[J].Nature,2017,550(7676):366-370.
[44]CHEN Q,SHE J,ZENG W,et al.Structure of mammalian endolysosomal TRPML1 channel in nanodiscs[J].Nature,2017,550(7676):415-418.
[45]HIRSCHI M,HERZIK M A JR,WIE J,et al.Cryoelectron microscopy structure of the lysosomal calciumpermeable channel TRPML3[J].Nature,2017,550(7676):411-414.
[46]ZHANG Z,TóTH B,SZOLLOSI A,et al.Structure of a TRPM2 channel in complex with Ca2+explains unique gating regulation[J/OL].Elife,2018,7:e36409.
[47]HUANG Y,WINKLER P A,SUN W,et al.Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium[J].Nature,2018,562(7725):145-149.
[48]WINKLER P A,HUANG Y,SUN W,et al.Electron cryo-microscopy structure of a human TRPM4 channel[J].Nature,2017,552(7684):200-204.
[49]GUO J,SHE J,ZENG W,et al.Structures of the calcium-activated,non-selective cation channel TRPM4[J].Nature,2017,552(7684):205-209.
[50]AUTZEN H E,MYASNIKOV A G,CAMPBELL M G,et al.Structure of the human TRPM4 ion channel in a lipid nanodisc[J].Science,2018,359(6372):228-232.
[51]DUAN J,LI Z,LI J,et al.Structure of full-length human TRPM4[J].Proc Natl Acad Sci U S A,2018,115(10):2377-2382.
[52]YIN Y,WU M,ZUBCEVIC L,et al.Structure of the cold-and menthol-sensing ion channel TRPM8[J].Science,2018,359(6372):237-241.
[53]TANG Q,GUO W,ZHENG L,et al.Structure of the receptor-activated human TRPC6 and TRPC3 ion channels[J].Cell Res,2018,28(7):746-755.
[54]FAN C,CHOI W,SUN W,et al.Structure of the human lipid-gated cation channel TRPC3[J/OL].Elife,2018,7:e36852.
[55]VINAYAGAM D,MAGER T,APELBAUM A,et al.Electron cryo-microscopy structure of the canonical TRPC4 ion channel[J/OL].Elife,2018,7:e36615.
[56]DUAN J,LI J,ZENG B,et al.Structure of the mouse TRPC4 ion channel[J].Nat Commun,2018,9(1):3102.
[57]JIN P,BULKLEY D,GUO Y,et al.Electron cryomicroscopy structure of the mechanotransduction channel NOMPC[J].Nature,2017,547(7661):118-122.
[58]SU Q,HU F,LIU Y,et al.Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1[J].Nat Commun,2018,9(1):1192.
[59]HULSE R E,LI Z,HUANG R K,et al.Cryo-EMstructure of the polycystin 2-l1 ion channel[J/OL].Elife,2018,7:e36931.
[2]YU F H,CATTERALL W A.The VGL-chanome:a protein superfamily specialized for electrical signaling and ionic homeostasis[J].Sci STKE,2004,2004(253):re15.
[3]JIANG Y,LEE A,CHEN J,et al.X-ray structure of a voltage-dependent K+channel[J].Nature,2003,423(6935):33-41.
[4]LONG S B,CAMPBELL E B,MACKINNON R.Crystal structure of a mammalian voltage-dependent shaker family K+channel[J].Science,2005,309(5736):897-903.
[5]LONG S B,CAMPBELL E B,MACKINNON R.Voltage sensor of Kv1.2:structural basis of electromechanical coupling[J].Science,2005,309(5736):903-908.
[6]LONG S B,TAO X,CAMPBELL E B,et al.Atomic structure of a voltage-dependent K+channel in a lipid membrane-like environment[J].Nature,2007,450(7168):376-382.
[7]WHICHER J R,MACKINNON R.Structure of the voltage-gated K+channel Eag1 reveals an alternative voltage sensing mechanism[J].Science,2016,353(6300):664-669.
[8]TAO X,HITE R K,MACKINNON R.Cryo-EMstructure of the open high-conductance Ca2+-activated K+channel[J].Nature,2017,541(7635):46-51.
[9]HITE R K,TAO X,MACKINNON R.Structural basis for gating the high-conductance Ca2+-activated K+channel[J].Nature,2017,541(7635):52-57.
[10]WANG W,MACKINNON R.Cryo-EM structure of the open human ether-à-go-go-related K+channel hERG[J].Cell,2017,169(3):422-430.e10.
[11]SUN J,MACKINNON R.Cryo-EM structure of a KCNQ1/CaM complex reveals insights into congenital long QT syndrome[J].Cell,2017,169(6):1042-1050.e9.
[12]ZHOU Y,MORAIS-CABRAL J H,KAUFMAN A,et al.Chemistry of ion coordination and hydration revealed by a K+channel-Fab complex at 2.0?resolution[J].Nature,2001,414(6859):43-48.
[13]YE S,LI Y,JIANG Y.Novel insights into K+selectivity from high-resolution structures of an open K+channel pore[J].Nat Struct Mol Biol,2010,17(8):1019-1023.
[14]SAUER D B,ZENG W,CANTY J,et al.Sodium and potassium competition in potassium-selective and nonselective channels[J].Nat Commun,2013,4:2721.
[15]TAO X,LEE A,LIMAPICHAT W,et al.A gating charge transfer center in voltage sensors[J].Science,2010,328(5974):67-73.
[16]TAKESHITA K,SAKATA S,YAMASHITA E,et al.X-ray crystal structure of voltage-gated proton channel[J].Nat Struct Mol Biol,2014,21(4):352-357.
[17]GUO J,ZENG W,CHEN Q,et al.Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana[J].Nature,2016,531(7593):196-201.
[18]PAYANDEH J,SCHEUER T,ZHENG N,et al.The crystal structure of a voltage-gated sodium channel[J].Nature,2011,475(7356):353-358.
[19]ZHANG X,REN W,DECAEN P,et al.Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel[J].Nature,2012,486(7401):130-134.
[20]PAYANDEH J,GAMAL E T M,SCHEUER T,et al.Crystal structure of a voltage-gated sodium channel in two potentially inactivated states[J].Nature,2012,486(7401):135-139.
[21]SULA A,BOOKER J,NG L C T,et al.The complete structure of an activated open sodium channel[J].Nat Commun,2017,8:14205.
[22]AHUJA S,MUKUND S,DENG L,et al.Structural basis of Nav1.7 inhibition by an isoform-selective smallmolecule antagonist[J].Science,2015,350(6267):aac5464.
[23]SHEN H,ZHOU Q,PAN X,et al.Structure of a eukaryotic voltage-gated sodium channel at near-atomic resolution[J].Science,2017,355(6328):eaal4326.
[24]SHEN H,LI Z,JIANG Y,et al.Structural basis for the modulation of voltage-gated sodium channels by animal toxins[J].Science,2018,362(6412):eaau2596.
[25]YAN Z,ZHOU Q,WANG L,et al.Structure of the Nav1.4-β1 complex from electric eel[J].Cell,2017,170(3):470-482.e11.
[26]PAN X,LI Z,ZHOU Q,et al.Structure of the human voltage-gated sodium channel Nav1.4 in complex withβ1[J].Science,2018,362(6412):eaau2486.
[27]NAYLOR C E,BAGNéRIS C,DECAEN P G,et al.Molecular basis of ion permeability in a voltage-gated sodium channel[J].EMBO J,2016,35(8):820-830.
[28]CLAPHAM D E,RUNNELS L W,STRüBING C.The TRP ion channel family[J].Nat Rev Neurosci,2001,2(6):387-396.
[29]CAO E,LIAO M,CHENG Y,et al.TRPV1 structures in distinct conformations reveal activation mechanisms[J].Nature,2013,504(7478):113-118.
[30]LIAO M,CAO E,JULIUS D,et al.Structure of the TRPV1 ion channel determined by electron cryomicroscopy[J].Nature,2013,504(7478):107-112.
[31]GAO Y,CAO E,JULIUS D,et al.TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action[J].Nature,2016,534(7607):347-351.
[32]PAULSEN C E,ARMACHE J P,GAO Y,et al.Structure of the TRPA1 ion channel suggests regulatory mechanisms[J].Nature,2015,525(7570):552.
[33]ZUBCEVIC L,HERZIK M A JR,CHUNG B C,et al.Cryo-electron microscopy structure of the TRPV2 ion channel[J].Nat Struct Mol Biol,2016,23(2):180-186.
[34]HUYNH K W,COHEN M R,JIANG J,et al.Structure of the full-length TRPV2 channel by cryo-EM[J].Nat Commun,2016,7:11130.
[35]ZUBCEVIC L,LE S,YANG H,et al.Conformational plasticity in the selectivity filter of the TRPV2 ion channel[J].Nat Struct Mol Biol,2018,25(5):405-415.
[36]DENG Z,PAKNEJAD N,MAKSAEV G,et al.CryoEM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms[J].Nat Struct Mol Biol,2018,25(3):252-260.
[37]TET H,LODOWSKI D T,HUYNH K W,et al.Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM[J].Nat Struct Mol Biol,2018,25(1):53-60.
[38]SAOTOME K,SINGH A K,YELSHANSKAYA M V,et al.Crystal structure of the epithelial calcium channel TRPV6[J].Nature,2016,534(7608):506-511.
[39]MCGOLDRICK L L,SINGH A K,SAOTOME K,et al.Opening of the human epithelial calcium channel TRPV6[J].Nature,2018,553(7687):233-237.
[40]SHEN P S,YANG X,DECAEN P G,et al.The structure of the polycystic kidney disease channel PKD2 in lipid nanodiscs[J].Cell,2016,167(3):763-773.e11.
[41]GRIEBEN M,PIKE A C W,SHINTRE C A,et al.Structure of the polycystic kidney disease TRP channel polycystin-2(PC2)[J].Nat Struct Mol Biol,2017,24(2):114-122.
[42]WILKES M,MADEJ M G,KREUTER L,et al.Molecular insights into lipid-assisted Ca2+regulation of the TRP channel polycystin-2[J].Nat Struct Mol Biol,2017,24(2):123-130.
[43]SCHMIEGE P,FINE M,BLOBEL G,et al.Human TRPML1 channel structures in open and closed conformations[J].Nature,2017,550(7676):366-370.
[44]CHEN Q,SHE J,ZENG W,et al.Structure of mammalian endolysosomal TRPML1 channel in nanodiscs[J].Nature,2017,550(7676):415-418.
[45]HIRSCHI M,HERZIK M A JR,WIE J,et al.Cryoelectron microscopy structure of the lysosomal calciumpermeable channel TRPML3[J].Nature,2017,550(7676):411-414.
[46]ZHANG Z,TóTH B,SZOLLOSI A,et al.Structure of a TRPM2 channel in complex with Ca2+explains unique gating regulation[J/OL].Elife,2018,7:e36409.
[47]HUANG Y,WINKLER P A,SUN W,et al.Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium[J].Nature,2018,562(7725):145-149.
[48]WINKLER P A,HUANG Y,SUN W,et al.Electron cryo-microscopy structure of a human TRPM4 channel[J].Nature,2017,552(7684):200-204.
[49]GUO J,SHE J,ZENG W,et al.Structures of the calcium-activated,non-selective cation channel TRPM4[J].Nature,2017,552(7684):205-209.
[50]AUTZEN H E,MYASNIKOV A G,CAMPBELL M G,et al.Structure of the human TRPM4 ion channel in a lipid nanodisc[J].Science,2018,359(6372):228-232.
[51]DUAN J,LI Z,LI J,et al.Structure of full-length human TRPM4[J].Proc Natl Acad Sci U S A,2018,115(10):2377-2382.
[52]YIN Y,WU M,ZUBCEVIC L,et al.Structure of the cold-and menthol-sensing ion channel TRPM8[J].Science,2018,359(6372):237-241.
[53]TANG Q,GUO W,ZHENG L,et al.Structure of the receptor-activated human TRPC6 and TRPC3 ion channels[J].Cell Res,2018,28(7):746-755.
[54]FAN C,CHOI W,SUN W,et al.Structure of the human lipid-gated cation channel TRPC3[J/OL].Elife,2018,7:e36852.
[55]VINAYAGAM D,MAGER T,APELBAUM A,et al.Electron cryo-microscopy structure of the canonical TRPC4 ion channel[J/OL].Elife,2018,7:e36615.
[56]DUAN J,LI J,ZENG B,et al.Structure of the mouse TRPC4 ion channel[J].Nat Commun,2018,9(1):3102.
[57]JIN P,BULKLEY D,GUO Y,et al.Electron cryomicroscopy structure of the mechanotransduction channel NOMPC[J].Nature,2017,547(7661):118-122.
[58]SU Q,HU F,LIU Y,et al.Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1[J].Nat Commun,2018,9(1):1192.
[59]HULSE R E,LI Z,HUANG R K,et al.Cryo-EMstructure of the polycystin 2-l1 ion channel[J/OL].Elife,2018,7:e36931.