Rhesus Monkey TRIM5α SPRY Domain Recognizes Multiple Epitopes That Span Several Capsid Monomers on the Surface of the HIV-1 Mature Viral Core

JOURNAL OF MOLECULAR BIOLOGY

卷:425

Article

Biris, Nikolaos^1,2  Tomashevski, Andrei^1,2  Bhattacharya, Akash^1,2  Diaz-Griffero, Felipe³  Ivanov, Dmitri N.^1,2 

[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[3] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

关键词: TRIM6 alpha;    HIV;    NMR;    SPRY;   

DOI  :  10.1016/j.jmb.2013.07.025

来源: Elsevier

【 摘 要 】

The restriction factor TRIM5 alpha binds to the capsid protein of the retroviral core and blocks retroviral replication. The affinity of TRIM5 alpha 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 TRIM5 alpha 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 TRIM5 alpha to capsid mutations, result in relatively low affinity of the individual SPRY domains for the capsid, and the TRIM5 alpha-mediated restriction depends on the avidity effect arising from the oligomerization of TRIM5 alpha. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

Free