Recognition of the HIV capsid by the TRIM5α restriction factor is mediated by a subset of pre-existing conformations of the TRIM5α SPRY domain.

ABSTRACT: The binding of the TRIM5α restriction factor to the HIV capsid is mediated by the C-terminal SPRY domain of TRIM5α. Atomic-level details of this host-pathogen interaction, which involves mobile variable loops of the SPRY domain, remain unclear. Some of the key determinants of restriction are encompassed by the long and disordered v1 loop of the SPRY domain. We applied molecular modeling to elucidate the conformational repertoire of the v1 loop and its role in the interaction with the capsid. All-atom replica exchange molecular dynamics revealed multiple transient, interconverting states of the v1 loop consistent with the intrinsic disorder observed experimentally. The docking of the SPRY conformations representing 10 most populated states onto the high-resolution model of the assembled HIV

SUBMITTER: Kovalskyy DB 

PROVIDER: S-EPMC4119003 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature