Article
- The EMBO Journal (2008) 27, 1411 - 1420
- doi:10.1038/emboj.2008.71
Published online: 10 April 2008
Subject Categories:
A molecular switch required for retrovirus assembly participates in the hexagonal immature lattice
Judith M Phillips1, Paul S Murray2, Diana Murray2 and Volker M Vogt1
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA
- Department of Pharmacology, Presbyterian Hospital, Mail Code: 7 West, Columbia University, New York, NY, USA
Correspondence to:
Volker M Vogt, Department of Molecular Biology & Genetics, Cornell University, 358 Biotech Building, Ithaca, NY 14853, USA. Tel.: +607 255 2443; Fax: +607 255 2428; E-mail: vmv1@cornell.edu
Received 25 October 2007; Accepted 12 March 2008
Abstract
In the Rous sarcoma virus (RSV) Gag protein, the 25 amino-acid residues of the p10 domain immediately upstream of the CA domain are essential for immature particle formation. We performed systematic mutagenesis on this region and found excellent correlation between the amino-acid side chains required for in vitro assembly and those that participate in the p10–CA dimer interface in a previously described crystal structure. We introduced exogenous cysteine residues that were predicted to form disulphide bonds across the dimer interface. Upon oxidation of immature particles, a disulphide-linked Gag hexamer was formed, implying that p10 participates in and stabilizes the immature Gag hexamer. This is the first example of a critical interaction between two different Gag domains. Molecular modeling of the RSV immature hexamer indicates that the N-terminal domains of CA must expand relative to the murine leukaemia virus mature hexamer to accommodate the p10 contact; this expansion is strikingly similar to recent cryotomography results for immature human immunodeficiency virus particles.
Keywords:
- Gag,
- HIV-1,
- Rous sarcoma virus,
- virus assembly
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