Rhesus monkey TRIM5α SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core

Nikolaos Biris, Andrei Tomashevski, Akash Bhattacharya, Felipe Diaz-Griffero, Dmitri N. Ivanov

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The restriction factor TRIM5α binds to the capsid protein of the retroviral core and blocks retroviral replication. The affinity of TRIM5α for the capsid is a major host tropism determinant of HIV and other primate immunodeficiency viruses, but the molecular interface involved in this host-pathogen interaction remains poorly characterized. Here we use NMR spectroscopy to investigate binding of the rhesus TRIM5α SPRY domain to a selection of HIV capsid constructs. The data are consistent with a model in which one SPRY domain interacts with more than one capsid monomer within the assembled retroviral core. The highly mobile SPRY v1 loop appears to span the gap between neighboring capsid hexamers making interhexamer contacts critical for restriction. The interaction interface is extensive, involves mobile loops and multiple epitopes, and lacks interaction hot spots. These properties, which may enhance resistance of TRIM5α to capsid mutations, result in relatively low affinity of the individual SPRY domains for the capsid, and the TRIM5α-mediated restriction depends on the avidity effect arising from the oligomerization of TRIM5α.

Original languageEnglish (US)
Pages (from-to)5032-5044
Number of pages13
JournalJournal of Molecular Biology
Volume425
Issue number24
DOIs
StatePublished - Dec 13 2013

Fingerprint

Capsid
Macaca mulatta
HIV-1
Epitopes
Viral Tropism
Primate Lentiviruses
HIV
Host-Pathogen Interactions
Capsid Proteins
B30.2-SPRY Domain
Magnetic Resonance Spectroscopy
Mutation

Keywords

  • HIV
  • NMR
  • SPRY
  • TRIM5α

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Rhesus monkey TRIM5α SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core. / Biris, Nikolaos; Tomashevski, Andrei; Bhattacharya, Akash; Diaz-Griffero, Felipe; Ivanov, Dmitri N.

In: Journal of Molecular Biology, Vol. 425, No. 24, 13.12.2013, p. 5032-5044.

Research output: Contribution to journalArticle

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