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

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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-08, Vol.109 (33), p.13278-13283
Main Authors: Biris, Nikolaos, Yang, Yang, Taylor, Alexander B., Tomashevski, Andrei, Guo, Miao, Hart, P. John, Diaz-Griffero, Felipe, Ivanov, Dmitri N.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Antibodies
Antigens
Biological Sciences
Capsid
Capsid - chemistry
Capsid - metabolism
Crystallography, X-Ray
Epitopes
Evolution, Molecular
HIV
HIV 1
HIV-1 - chemistry
Macaca mulatta - metabolism
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Sequence Data
Primates
Protein Binding
Protein Interaction Mapping
Protein Structure, Tertiary
Proteins
Proteins - chemistry
Proteins - metabolism
Retroviridae
Surface Properties
Titration
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1203536109