View source for 2jrd


==Influenza Hemagglutinin Fusion Domain Mutant F9A==
<StructureSection load='2jrd' size='340' side='right'caption='[[2jrd]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jrd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Influenza_A_virus Influenza A virus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JRD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JRD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2jrd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jrd OCA], [https://pdbe.org/2jrd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jrd RCSB], [https://www.ebi.ac.uk/pdbsum/2jrd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jrd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A2Y1_9INFA A0A2Y1_9INFA] 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 either through clathrin-dependent endocytosis or through 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.[HAMAP-Rule:MF_04072]  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.[RuleBase:RU003324]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have previously identified Trp(14) as a critical residue that stabilizes the kink in the boomerang structure of the influenza fusion domain and found that cells expressing hemagglutinin with a Trp(14) to Ala mutation cannot fuse with red blood cells. However, mutating another aromatic residue, Phe(9), on the other side of the kink did not have a significant effect on fusion or the ability of the mutant fusion peptide to bind to or perturb the bilayer structure of lipid model membranes. We reasoned that Phe is not as potent to contribute to the kink as the larger Trp and that the cooperation of Phe(9) and Ile(10) might be needed to elicit the same effect. Indeed, the double mutant F9A/I10A diminished cell-cell fusion and the ability of the fusion domain to bind to and perturb lipid bilayers in a similar fashion as the W14A mutant. A structure determination of F9A in lipid micelles by solution NMR shows that F9A adopts a similarly kinked structure as wild type. Distances between the two arms of the boomerang structure of wild type, F9A, W14A, and F9A/I10A in lipid bilayers were measured by double electron-electron resonance spectroscopy and showed that the kinks of W14A and F9A/I10A are more flexible than those of wild type and F9A. These results underscore the importance of large hydrophobic residues on both sides of the kink region of the influenza hemagglutinin fusion domain to fix the angle of the boomerang structure and thereby confer fusion function to this critical domain.

Locking the kink in the influenza hemagglutinin fusion domain structure.,Lai AL, Tamm LK J Biol Chem. 2007 Aug 17;282(33):23946-56. Epub 2007 Jun 12. PMID:17567572<ref>PMID:17567572</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2jrd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Hemagglutinin 3D structures|Hemagglutinin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Influenza A virus]]
[[Category: Large Structures]]
[[Category: Lai AL]]
[[Category: Tamm LK]]