Influenza M2 proton channels.
M2 of the influenza virus is an intriguing transmembrane protein that forms a minuscule proton channel in the viral envelope. Its recognized function is to equilibrate pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation. It is vital for viral replication and it is a target for the anti-influenza drugs, amantadine and rimantadine. Recently, high resolution structures of M2 channels of both flu A and B have been obtained, providing the desperately needed structural details for understanding the mechanism of proton conductance. In particular, the establishment of the functional solution NMR system of the proton channels enabled simultaneous high resolution structure characterization and measurement of channel dynamics coupled to channel activity. This review summarizes our current understanding of how protons are conducted through the M2 channel from a structural point of view, as well as the modes by which important channel gating elements function during proton conduction.
Pielak
Rafal M
RM
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Chou
James J
JJ
D018360:Crystallography, X-Ray; D004553:Electric Conductivity; D006639:Histidine / Q000737:chemistry; D009980:Influenza A virus / Q000737:chemistry*; D009981:Influenza B virus / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011522:Protons; D055672:Static Electricity; D014364:Tryptophan / Q000737:chemistry; D014763:Viral Matrix Proteins / Q000737:chemistry*; D000086082:Viroporin Proteins
D006639:Histidine; D007473:Ion Channels; D011522:Protons; D014364:Tryptophan; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
Physiol Rev. 2003 Apr;83(2):475-579
12663866
Science. 1993 Nov 26;262(5138):1401-7
8248779
J Biol Chem. 2002 Oct 18;277(42):39880-6
12183461
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7379-84
19383794
Virology. 2003 Feb 1;306(1):7-17
12620792
Protein Sci. 2001 Nov;10(11):2241-50
11604531
Virology. 1991 Jul;183(1):32-43
2053285
Cell. 1985 Mar;40(3):627-33
3882238
Virology. 1991 Feb;180(2):617-24
1989386
Nature. 2008 Jan 31;451(7178):591-5
18235503
Biochemistry. 2000 Nov 21;39(46):14160-70
11087364
Acc Chem Res. 2002 Jun;35(6):366-75
12069621
J Virol. 1991 Jan;65(1):232-44
1985199
Biophys J. 2000 Aug;79(2):767-75
10920010
Biochemistry. 2001 May 22;40(20):6053-60
11352741
J Biol Chem. 2006 Apr 7;281(14):8997-9000
16407184
Virology. 1999 Feb 1;254(1):196-209
9927586
Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11301-6
9326604
Biophys J. 2007 Jun 15;92(12):4335-43
17384070
J Virol. 1988 Aug;62(8):2762-72
2455818
J Mol Biol. 1999 Feb 26;286(3):951-62
10024461
EMBO J. 1985 Nov;4(11):3021-4
4065098
Biophys J. 1997 Nov;73(5):2511-7
9370444
FEBS Lett. 2003 Sep 18;552(1):35-8
12972149
Vaccine. 2008 Sep 12;26 Suppl 4:D49-53
19230160
J Virol. 2006 Aug;80(16):8178-89
16873274
J Virol. 2004 Oct;78(20):11007-15
15452221
J Biochem. 2009 Apr;145(4):543-54
19155268
Nat Struct Biol. 1997 Mar;4(3):239-44
9164466
Arch Virol. 2009;154(10):1619-24
19763781
EMBO J. 1990 Nov;9(11):3469-76
2209554
Nat Struct Mol Biol. 2009 Dec;16(12):1267-71
19898475
Biochemistry. 2002 Sep 17;41(37):11294-300
12220196
J Virol. 2008 Jan;82(2):728-39
17989175
J Virol. 1999 Dec;73(12):9695-701
10559278
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9280-5
12883000
J Virol. 2008 Oct;82(20):10059-70
18701586
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W512-21
17526523
Nature. 2008 Jan 31;451(7178):596-9
18235504
Cell. 1992 May 15;69(4):577-8
1375129
J Mol Biol. 2000 Jan 7;295(1):117-25
10623512
Cell. 1998 Jul 24;94(2):171-80
9695946
Proc Natl Acad Sci U S A. 2006 May 2;103(18):6865-70
16632600
Biophys J. 1995 Oct;69(4):1363-71
8534806
Protein Sci. 2003 Nov;12(11):2597-605
14573870
Biochim Biophys Acta. 2000 May 12;1458(1):104-19
10812027
Dev Cell. 2003 Jul;5(1):175-84
12852861
J Virol. 2003 Oct;77(19):10630-7
12970447