M2 protein

Function

The M2 protein or Matrix protein 2 (M2) is a proton selective ion channel of the influenza virus^[1]. It is activated by low pH. M2 has 3 domains: an ectodomain, transmembrane domain (TM) and a C terminal cytoplasmic domain. See more in:
M2 Proton Channel
Molecular Playground/Influenza A M2 transmembrane domain
M2 Proton Channel Inhibitor Pharmacokinetics.

Structural highlights

M2 protein from Human respiratory syncytial virus contains 4 domains: Zn-binding, transmembrane (TM), core which binds RNA and a C terminal domain^[2]. .

3D structures of M2 protein

Updated on 05-November-2025

3bkd, 4qk7, 4qkc, 4qkl, 4qkm, 5joo, 5ttc, 5um1, 6mpl, 6mpm, 6mpn - IavM2 TM – Influenza A virus

3lbw, 4rwb, 4rwc, 5c02 – IavM2 TM (mutant)
3c9j, 6bkk, 6bmz - IavM2 TM + amantadine derivative
6oug - IavM2 TM (mutant) + amantadine derivative
6bkl, 6boc - IavM2 TM + rimantadine
2rlf - IavM2 TM +rimantadine - NMR
1mp6, 1nyj, 2h95, 2kqt - IavM2 TM – NMR
2kih, 2kwx, 2l0j - IavM2 TM (mutant) – NMR
2ljb, 2ljc - IavM2 TM (mutant)/IbvM2 TM – NMR
2kix - IbvM2 TM (mutant) – Influenza B virus – NMR
2kj1 – IbvM2 cytoplasmic domain - NMR
4c3b, 4c3d – hrsvM2 – Human respiratory syncytial virus
4c3e – hrsvM2 (mutant)
5nkx – hrsvM2 core domain 73-185
2l9j – hrsvM2 core domain (mutant) - NMR
6g0y – hrsvM2 + phosphoprotein
6pzq – hrsvM2 + RNA
5hyu – M2 residues 42-142 + C4B-binding protein alpha chain – Steptococcus pyogenes

References

1. ↑ Betakova T. M2 protein-a proton channel of influenza A virus. Curr Pharm Des. 2007;13(31):3231-5. PMID:18045172
2. ↑ Tanner SJ, Ariza A, Richard CA, Kyle HF, Dods RL, Blondot ML, Wu W, Trincao J, Trinh CH, Hiscox JA, Carroll MW, Silman NJ, Eleouet JF, Edwards TA, Barr JN. Crystal structure of the essential transcription antiterminator M2-1 protein of human respiratory syncytial virus and implications of its phosphorylation. Proc Natl Acad Sci U S A. 2014 Jan 16. PMID:24434552 doi:http://dx.doi.org/10.1073/pnas.1317262111