6MJH
The S31N mutant of the influenza A M2 proton channel in two distinct conformational states
Summary for 6MJH
| Entry DOI | 10.2210/pdb6mjh/pdb |
| Descriptor | Matrix protein 2, CALCIUM ION, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | viral protein, proton channel, s31n, membrane protein |
| Biological source | Influenza A virus (A/pigeon/Jiangsu/K23/2013(H9N2)) |
| Total number of polymer chains | 8 |
| Total formula weight | 22446.69 |
| Authors | Thomaston, J.L.,DeGrado, W.F. (deposition date: 2018-09-20, release date: 2019-06-26, Last modification date: 2024-11-06) |
| Primary citation | Thomaston, J.L.,Wu, Y.,Polizzi, N.,Liu, L.,Wang, J.,DeGrado, W.F. X-ray Crystal Structure of the Influenza A M2 Proton Channel S31N Mutant in Two Conformational States: An Open and Shut Case. J.Am.Chem.Soc., 141:11481-11488, 2019 Cited by PubMed Abstract: The amantadine-resistant S31N mutant of the influenza A M2 proton channel has become prevalent in currently circulating viruses. Here, we have solved an X-ray crystal structure of M2(22-46) S31N that contains two distinct conformational states within its asymmetric unit. This structure reveals the mechanism of adamantane resistance in both conformational states of the M2 channel. In the Inward conformation, the mutant Asn31 side chain faces the channel pore and sterically blocks the adamantane binding site. In the Inward conformation, Asn31 forms hydrogen bonds with carbonyls at the monomer-monomer interface, which twists the monomer helices and constricts the channel pore at the drug binding site. We also examine M2(19-49) WT and S31N using solution NMR spectroscopy and show that distribution of the two conformational states is dependent on both detergent choice and experimental pH. PubMed: 31184871DOI: 10.1021/jacs.9b02196 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.06 Å) |
Structure validation
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