3C9J

The Crystal structure of Transmembrane domain of M2 protein and Amantadine complex

Summary for 3C9J

• Entry DOI: 10.2210/pdb3c9j/pdb
• Descriptor: Proton Channel protein M2, transmembrane segment, (3S,5S,7S)-tricyclo[3.3.1.1~3,7~]decan-1-amine (2 entities in total)
• Functional Keywords: proton channel, ion channel, m2tm, m2-amantadine complex, membrane protein
• Cellular location: Virion membrane (By similarity): O70632
• Total number of polymer chains: 4
• Total formula weight: 11128.53

Authors

Stouffer, A.L.,Acharya, R.,Salom, D. (deposition date: 2008-02-15, release date: 2008-03-11, Last modification date: 2024-04-03)

Primary citation

Stouffer, A.L.,Acharya, R.,Salom, D.,Levine, A.S.,Costanzo, L.D.,Soto, C.S.,Tereshko, V.,Nanda, V.,Stayrook, S.,DeGrado, W.F.
Structural basis for the function and inhibition of an influenza virus proton channel
Nature, 451:596-600, 2008

PubMed Abstract: The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.

PubMed: 18235504
DOI: 10.1038/nature06528

Experimental method

X-RAY DIFFRACTION (3.5 Å)