2ljb

From Proteopedia

Structure of the influenza AM2-BM2 chimeric channel

Structural highlights

2ljb is a 4 chain structure with sequence from Influenza A virus H3N2 and Influenza B virus (B/Taiwan/70061/2006). Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B4UQM4_9INFB Q9YP62_9INFA Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation (By similarity).[SAAS:SAAS002089_004_400258]

Publication Abstract from PubMed

The M2 channel of influenza A is a target of the adamantane family antiviral drugs. Two different drug-binding sites have been reported: one inside the pore, and the other is a lipid-facing pocket. A previous study showed that a chimera of M2 variants from influenza A and B that contains only the pore-binding site is sensitive to amantadine inhibition, suggesting that the primary site of inhibition is inside the pore. To obtain atomic details of channel-drug interaction, we determined the structures of the chimeric channel with and without rimantadine. Inside the channel and near the N-terminal end, methyl groups of Val27 and Ala30 from four subunits form a hydrophobic pocket around the adamantane, and the drug amino group appears to be in polar contact with the backbone oxygen of Ala30. The structures also reveal differences between the drug-bound and -unbound states of the channel that can explain drug resistance.

Structural investigation of rimantadine inhibition of the AM2-BM2 chimera channel of influenza viruses.,Pielak RM, Oxenoid K, Chou JJ Structure. 2011 Nov 9;19(11):1655-63. PMID:22078564^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pielak RM, Oxenoid K, Chou JJ. Structural investigation of rimantadine inhibition of the AM2-BM2 chimera channel of influenza viruses. Structure. 2011 Nov 9;19(11):1655-63. PMID:22078564 doi:10.1016/j.str.2011.09.003