4QKM

Influenza A M2 wild type TM domain at low pH in the lipidic cubic phase under room temperature diffraction conditions

Summary for 4QKM

• Entry DOI: 10.2210/pdb4qkm/pdb
• Related: 4QK6 4QK7 4QKC 4QKL
• Descriptor: influenza M2 monomer, CALCIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: transmembrane alpha helix, ph-activated proton channel, viral protein
• Biological source: Influenza A virus
• Cellular location: Virion membrane : W8PGZ1
• Total number of polymer chains: 1
• Total formula weight: 3288.56

Authors

Thomaston, J.L.,DeGrado, W.F. (deposition date: 2014-06-06, release date: 2015-11-11, Last modification date: 2024-11-06)

Primary citation

Thomaston, J.L.,Alfonso-Prieto, M.,Woldeyes, R.A.,Fraser, J.S.,Klein, M.L.,Fiorin, G.,DeGrado, W.F.
High-resolution structures of the M2 channel from influenza A virus reveal dynamic pathways for proton stabilization and transduction.
Proc.Natl.Acad.Sci.USA, 112:14260-14265, 2015

PubMed Abstract: The matrix 2 (M2) protein from influenza A virus is a proton channel that uses His37 as a selectivity filter. Here we report high-resolution (1.10 Å) cryogenic crystallographic structures of the transmembrane domain of M2 at low and high pH. These structures reveal that waters within the pore form hydrogen-bonded networks or "water wires" spanning 17 Å from the channel entrance to His37. Pore-lining carbonyl groups are well situated to stabilize hydronium via second-shell interactions involving bridging water molecules. In addition, room temperature crystallographic structures indicate that water becomes increasingly fluid with increasing temperature and decreasing pH, despite the higher electrostatic field. Complementary molecular dynamics simulations reveal a collective switch of hydrogen bond orientations that can contribute to the directionality of proton flux as His37 is dynamically protonated and deprotonated in the conduction cycle.

PubMed: 26578770
DOI: 10.1073/pnas.1518493112

Experimental method

X-RAY DIFFRACTION (1.44 Å)