Rhesus monkey TRIM5? SPRY domain recognizes multiple epitopes that span several capsid monomers on the surface of the HIV-1 mature viral core.

ABSTRACT: The restriction factor TRIM5? binds to the capsid protein of the retroviral core and blocks retroviral replication. The affinity of TRIM5? 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? 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? to capsid mutations, result in relatively low affinity of the individual SPRY domains for the capsid, and the TRIM5?-mediated restriction depends on the avidity effect arising from the oligomerization of TRIM5?.

SUBMITTER: Biris N 

PROVIDER: S-EPMC4116666 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature