1ibo

From Proteopedia

NMR STRUCTURE OF HEMAGGLUTININ FUSION PEPTIDE IN DPC MICELLES AT PH 7.4

PDB ID 1ibo

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Structural highlights

1ibo is a 1 chain structure with sequence from Influenza A virus (A/duck/Ukraine/1/1963(H3N8)). 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

HEMA_I63A3 Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore.

Publication Abstract from PubMed

The N-terminal domain of the influenza hemagglutinin (HA) is the only portion of the molecule that inserts deeply into membranes of infected cells to mediate the viral and the host cell membrane fusion. This domain constitutes an autonomous folding unit in the membrane, causes hemolysis of red blood cells and catalyzes lipid exchange between juxtaposed membranes in a pH-dependent manner. Combining NMR structures determined at pHs 7.4 and 5 with EPR distance constraints, we have deduced the structures of the N-terminal domain of HA in the lipid bilayer. At both pHs, the domain is a kinked, predominantly helical amphipathic structure. At the fusogenic pH 5, however, the domain has a sharper bend, an additional 3(10)-helix and a twist, resulting in the repositioning of Glu 15 and Asp 19 relative to that at the nonfusogenic pH 7.4. Rotation of these charged residues out of the membrane plane creates a hydrophobic pocket that allows a deeper insertion of the fusion domain into the core of the lipid bilayer. Such an insertion mode could perturb lipid packing and facilitate lipid mixing between juxtaposed membranes.

Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin.,Han X, Bushweller JH, Cafiso DS, Tamm LK Nat Struct Biol. 2001 Aug;8(8):715-20. PMID:11473264^[1]

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

References

↑ Han X, Bushweller JH, Cafiso DS, Tamm LK. Membrane structure and fusion-triggering conformational change of the fusion domain from influenza hemagglutinin. Nat Struct Biol. 2001 Aug;8(8):715-20. PMID:11473264 doi:10.1038/90434