Transitions to and from the CD4-bound conformation are modulated by a single-residue change in the human immunodeficiency virus type 1 gp120 inner domain

Aemro Kassa, Navid Madani, Arne Schön, Hillel Haim, Andrés Finzi, Shi Hua Xiang, Liping Wang, Amy Princiotto, Marie Pancera, Joel Courter, Amos B. Smith, Ernesto Freire, Peter D. Kwong, Joseph Sodroski

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Binding to the primary receptor CD4 induces conformational changes in the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding to the coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by the gp41 transmembrane envelope glycoprotein. Here we report the derivation of an HIV-1 gp120 variant, H66N, that confers envelope glycoprotein resistance to temperature extremes. The H66N change decreases the spontaneous sampling of the CD4-bound conformation by the HIV-1 envelope glycoproteins, thus diminishing CD4-independent infection. The H66N change also stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved, decreasing the probability of CD4-induced inactivation and revealing the enhancing effects of soluble CD4 binding on HIV-1 infection. In the CD4-bound conformation, the highly conserved histidine 66 is located between the receptor-binding and gp41-interactive surfaces of gp120. Thus, a single amino acid change in this strategically positioned gp120 inner domain residue influences the propensity of the HIV-1 envelope glycoproteins to negotiate conformational transitions to and from the CD4-bound state.

Original languageEnglish (US)
Pages (from-to)8364-8378
Number of pages15
JournalJournal of virology
Volume83
Issue number17
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Transitions to and from the CD4-bound conformation are modulated by a single-residue change in the human immunodeficiency virus type 1 gp120 inner domain'. Together they form a unique fingerprint.

  • Cite this

    Kassa, A., Madani, N., Schön, A., Haim, H., Finzi, A., Xiang, S. H., Wang, L., Princiotto, A., Pancera, M., Courter, J., Smith, A. B., Freire, E., Kwong, P. D., & Sodroski, J. (2009). Transitions to and from the CD4-bound conformation are modulated by a single-residue change in the human immunodeficiency virus type 1 gp120 inner domain. Journal of virology, 83(17), 8364-8378. https://doi.org/10.1128/JVI.00594-09