title: Binding of the rhesus TRIM5α PRYSPRY domain to capsid is necessary but not sufficient for HIV-1 restriction.
abstract: The PRYSPRY domain of TRIM5α provides specificity and the capsid recognition motif to retroviral restriction. Restriction of HIV-1 by rhesus TRIM5α (TRIM5αrh) has been correlated to its ability to bind to the HIV-1 core, suggesting that capsid binding is required for restriction. This work explores whether the PRYSPRY domain of TRIM5αrh exhibits an additional function besides binding to the HIV-1 core. Using our recently described structure of the PRYSPRY domain, we performed an exhaustive structure-function study of the surface and interior residues of the PRYSPRY domain. Testing retroviral restriction and capsid binding of an extensive collection of 60 TRIM5αrh PRYSPRY variants revealed that binding is necessary but not sufficient for restriction. In support of this hypothesis, we showed that some human tripartite motif proteins bind the HIV-1 capsid but do not restrict HIV-1 infection, such as human TRIM6 and TRIM34. Overall this work suggested that the PRYSPRY domain serves an unknown function, distinct from the binding of TRIM5αrh to the HIV-1 core, to block HIV-1 infection.
authors: Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1301 Morris Park-Price Center 501, Bronx, NY 10461, USA.
authors: Yang
authors: Y
authors: Yang
authors: Alberto
authors: A
authors: Brandariz-Nuñez
authors: Thomas
authors: T
authors: Fricke
authors: Dmitri N
authors: DN
authors: Ivanov
authors: Zoe
authors: Z
authors: Sarnak
authors: Felipe
authors: F
authors: Diaz-Griffero
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Capsid; HIV-1; PRYSPRY; Restriction; TRIM5; V1 loop