Structure of the rhesus monkey TRIM5α PRYSPRY domain, the HIV capsid recognition module

Nikolaos Biris, Yang Yang, Alexander B. Taylor, Andrei Tomashevski, Miao Guo, P. John Hart, Felipe Diaz-Griffero, Dmitri N. Ivanov

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Tripartite motif protein TRIM5α blocks retroviral replication after cell entry, and species-specific differences in its activity are determined by sequence variations within the C-terminal B30.2/ PRYSPRY domain. Here we report a high-resolution structure of a TRIM5α PRYSPRY domain, the PRYSPRY of the rhesus monkey TRIM5α that potently restricts HIV infection, and identify features involved in its interaction with the HIV capsid. The extensive capsidbinding interface maps on the structurally divergent face of the protein formed by hypervariable loop segments, confirming that TRIM5α evolution is largely determined by its binding specificity. Interactions with the capsid are mediated by flexible variable loops via a mechanism that parallels antigen recognition by IgM antibodies, a similarity that may help explain some of the unusual functional properties of TRIM5α. Distinctive features of this pathogenrecognition interface, such as structural plasticity conferred by the mobile v1 segment and interaction with multiple epitopes, may allow restriction of divergent retroviruses and increase resistance to capsid mutations.

Original languageEnglish (US)
Pages (from-to)13278-13283
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number33
DOIs
StatePublished - Aug 14 2012

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Capsid
Macaca mulatta
HIV
Retroviridae
HIV Infections
Immunoglobulin M
Epitopes
Antigens
Mutation
Antibodies
B30.2-SPRY Domain
Proteins

ASJC Scopus subject areas

  • General

Cite this

Structure of the rhesus monkey TRIM5α PRYSPRY domain, the HIV capsid recognition module. / Biris, Nikolaos; Yang, Yang; Taylor, Alexander B.; Tomashevski, Andrei; Guo, Miao; Hart, P. John; Diaz-Griffero, Felipe; Ivanov, Dmitri N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 33, 14.08.2012, p. 13278-13283.

Research output: Contribution to journalArticle

Biris, Nikolaos ; Yang, Yang ; Taylor, Alexander B. ; Tomashevski, Andrei ; Guo, Miao ; Hart, P. John ; Diaz-Griffero, Felipe ; Ivanov, Dmitri N. / Structure of the rhesus monkey TRIM5α PRYSPRY domain, the HIV capsid recognition module. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 33. pp. 13278-13283.
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