1F23

CONTRIBUTION OF A BURIED HYDROGEN BOND TO HIV-1 ENVELOPE GLYCOPROTEIN STRUCTURE AND FUNCTION

Summary for 1F23

• Entry DOI: 10.2210/pdb1f23/pdb
• Descriptor: TRANSMEMBRANE GLYCOPROTEIN (2 entities in total)
• Functional Keywords: hiv-1 envelope protein, gp41, membrane fusion, hiv-1 entry, viral protein
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 52924.73

Authors

Liu, J.,Shu, W.,Fagan, M.,Nunberg, J.H.,Lu, M. (deposition date: 2000-05-23, release date: 2001-06-20, Last modification date: 2024-02-07)

Primary citation

Liu, J.,Shu, W.,Fagan, M.B.,Nunberg, J.H.,Lu, M.
Structural and functional analysis of the HIV gp41 core containing an Ile573 to Thr substitution: implications for membrane fusion.
Biochemistry, 40:2797-2807, 2001

PubMed Abstract: 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.

PubMed: 11258890
DOI: 10.1021/bi0024759

Experimental method

X-RAY DIFFRACTION (2.3 Å)