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| [[Image:1f23.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_1f23| PDB=1f23 | SCENE= }} | | {{STRUCTURE_1f23| PDB=1f23 | SCENE= }} |
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| '''CONTRIBUTION OF A BURIED HYDROGEN BOND TO HIV-1 ENVELOPE GLYCOPROTEIN STRUCTURE AND FUNCTION'''
| | ===CONTRIBUTION OF A BURIED HYDROGEN BOND TO HIV-1 ENVELOPE GLYCOPROTEIN STRUCTURE AND FUNCTION=== |
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| ==Overview==
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| The envelope glycoprotein of HIV-1 consists of the surface subunit gp120 and the transmembrane subunit gp41. Binding of gp120 to target cell receptors induces a conformational change in gp41, which then mediates the fusion of viral and cellular membranes. A buried isoleucine (Ile573) in a central trimeric coiled coil within the fusion-active gp41 ectodomain core is thought to favor this conformational activation. The role of Ile573 in determining the structure and function of the gp120-gp41 complex was investigated by mutating this residue to threonine, a nonconservative substitution in HIV-1 that occurs naturally in SIV. While the introduction of Thr573 markedly destabilized the gp41 core, the three-dimensional structure of the mutant trimer of hairpins was very similar to that of the wild-type molecule. A new hydrogen-bonding interaction between the buried Thr573 and Thr569 residues appears to allow formation of the trimer-of-hairpins structure at physiological temperature. The mutant envelope glycoprotein expressed in 293T cells and incorporated within pseudotyped virions displayed only a moderate reduction in syncytium-inducing capacity and virus infectivity, respectively. Our results demonstrate that the proper folding of the gp41 core underlies the membrane fusion properties of the gp120-gp41 complex. An understanding of the gp41 activation process may suggest novel strategies for vaccine and antiviral drug development.
| | The line below this paragraph, {{ABSTRACT_PUBMED_11258890}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 11258890 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_11258890}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Hiv-1 envelope protein]] | | [[Category: Hiv-1 envelope protein]] |
| [[Category: Membrane fusion]] | | [[Category: Membrane fusion]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:47:43 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 02:21:35 2008'' |
