Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

Zhao, G and Ke, D and Vu, T and Ahn, J and Shah, VB and Yang, R and Aiken, C and Charlton, LM and Gronenborn, AM and Zhang, P (2011) Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces. PLoS Pathogens, 7 (3). ISSN 1553-7366

Published Version
Available under License : See the attached license file.

Download (2MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)


TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al.


Social Networking:
Share |


Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Zhao, Ggoz1@pitt.eduGOZ1
Ke, D
Vu, T
Ahn, Jjia12@pitt.eduJIA12
Shah, VB
Yang, R
Aiken, C
Charlton, LM
Gronenborn, AMamg100@pitt.eduAMG100
Zhang, PPEZ7@pitt.eduPEZ7
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 March 2011
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 7
Number: 3
DOI or Unique Handle: 10.1371/journal.ppat.1002009
Schools and Programs: School of Medicine > Structural Biology
Refereed: Yes
ISSN: 1553-7366
MeSH Headings: Animals; Capsid--metabolism; Capsid Proteins--metabolism; Carrier Proteins--metabolism; HIV-1--immunology; HIV-1--metabolism; HIV-1--pathogenicity; Host-Pathogen Interactions; Humans; Macaca mulatta; Membrane Transport Proteins--metabolism; Protein Binding; Protein Structure, Tertiary; Proteins--metabolism; Sequence Homology, Amino Acid; Species Specificity; Zinc Fingers
Other ID: NLM PMC3063768
PubMed Central ID: PMC3063768
PubMed ID: 21455494
Date Deposited: 30 Aug 2012 14:31
Last Modified: 22 Jun 2021 15:55


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item