3LBW

High resolution crystal structure of transmembrane domain of M2

Summary for 3LBW

• Entry DOI: 10.2210/pdb3lbw/pdb
• Descriptor: M2 protein, 4-bromobenzoic acid, DI(HYDROXYETHYL)ETHER, ... (5 entities in total)
• Functional Keywords: proton channel, m2tm, influenza a virus m2 protein, host cell membrane, hydrogen ion transport, ionic channel, transmembrane, virion, transport protein
• Biological source: influenza A virus
• Total number of polymer chains: 4
• Total formula weight: 11086.91

Authors

Acharya, R.,Polishchuk, A.L.,DeGrado, W.F. (deposition date: 2010-01-08, release date: 2010-07-28, Last modification date: 2023-09-06)

Primary citation

Acharya, R.,Carnevale, V.,Fiorin, G.,Levine, B.G.,Polishchuk, A.L.,Balannik, V.,Samish, I.,Lamb, R.A.,Pinto, L.H.,DeGrado, W.F.,Klein, M.L.
Structure and mechanism of proton transport through the transmembrane tetrameric M2 protein bundle of the influenza A virus.
Proc.Natl.Acad.Sci.USA, 107:15075-15080, 2010

PubMed Abstract: The M2 proton channel from influenza A virus is an essential protein that mediates transport of protons across the viral envelope. This protein has a single transmembrane helix, which tetramerizes into the active channel. At the heart of the conduction mechanism is the exchange of protons between the His37 imidazole moieties of M2 and waters confined to the M2 bundle interior. Protons are conducted as the total charge of the four His37 side chains passes through 2(+) and 3(+) with a pK(a) near 6. A 1.65 A resolution X-ray structure of the transmembrane protein (residues 25-46), crystallized at pH 6.5, reveals a pore that is lined by alternating layers of sidechains and well-ordered water clusters, which offer a pathway for proton conduction. The His37 residues form a box-like structure, bounded on either side by water clusters with well-ordered oxygen atoms at close distance. The conformation of the protein, which is intermediate between structures previously solved at higher and lower pH, suggests a mechanism by which conformational changes might facilitate asymmetric diffusion through the channel in the presence of a proton gradient. Moreover, protons diffusing through the channel need not be localized to a single His37 imidazole, but instead may be delocalized over the entire His-box and associated water clusters. Thus, the new crystal structure provides a possible unification of the discrete site versus continuum conduction models.

PubMed: 20689043
DOI: 10.1073/pnas.1007071107

Experimental method

X-RAY DIFFRACTION (1.65 Å)