title: Second site reversion of a mutation near the amino terminus of the HIV-1 capsid protein.
abstract: During HIV-1 morphogenesis, the precursor Gag protein is processed to release capsid (CA) proteins that form the mature virus core. In this process, the CA proteins assemble a lattice in which N-terminal domain (NTD) helices 1-3 are critical for multimer formation. Mature core assembly requires refolding of the N-terminus of CA into a β-hairpin, but the precise contribution of the hairpin core morphogenesis is unclear. We found that mutations at isoleucine 15 (I15), between the β-hairpin and NTD helix 1 are incompatible with proper mature core assembly. However, a compensatory mutation of histidine 12 in the β-hairpin to a tyrosine was selected by long term passage of an I15 mutant virus in T cells. The tyrosine does not interact directly with residue 15, but with NTD helix 3, supporting a model in which β-hairpin folding serves to align helix 3 for mature NTD multimerization.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA. Electronic address: lopezcl@ohsu.edu.
authors.forename: Claudia S
authors.initials: CS
authors.lastname: López
authors.forename: Seyram M
authors.initials: SM
authors.lastname: Tsagli
authors.forename: Rachel
authors.initials: R
authors.lastname: Sloan
authors.forename: Jacob
authors.initials: J
authors.lastname: Eccles
authors.forename: Eric
authors.initials: E
authors.lastname: Barklis
mesh_terms: D019943:Amino Acid Substitution; D002460:Cell Line; D016655:HIV Core Protein p24 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D011487:Protein Conformation; D017510:Protein Folding; D055503:Protein Multimerization; D013489:Suppression, Genetic; D019065:Virus Assembly
chemical_list: D016655:HIV Core Protein p24
keywords: Capsid; Gag; HIV; N-terminal domain; Virus assembly