17 research outputs found
Toxoplasma gondii and the Immunity-Related GTPase (IRG) resistance system in mice: a review
Infantile Cervical Intramedullary Cavernous Angioma Manifesting as Hematomyelia -Case Report-
Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia Symbiont Fitness
SAMHD1 transcript upregulation during SIV infection of the central nervous system does not associate with reduced viral load
Cofactor-Independent Phosphoglycerate Mutase from Nematodes Has Limited Druggability, as Revealed by Two High-Throughput Screens
Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G
The human APOBEC3G (A3G) DNA cytosine deaminase restricts and hypermutates DNA-based parasites including HIV-1. The viral infectivity factor (Vif) prevents restriction by triggering A3G degradation. Although the structure of the A3G catalytic domain is known, the structure of the N-terminal Vif-binding domain has proven more elusive. Here, we used evolution- and structure-guided mutagenesis to solubilize the Vif-binding domain of A3G, thus permitting structural determination by NMR spectroscopy. A smaller zinc-coordinating pocket and altered helical packing distinguish the structure from previous catalytic-domain structures and help to explain the reported inactivity of this domain. This soluble A3G N-terminal domain is bound by Vif; this enabled mutagenesis and biochemical experiments, which identified a unique Vif-interacting surface formed by the alpha1-beta1, beta2-alpha2 and beta4-alpha4 loops. This structure sheds new light on the Vif-A3G interaction and provides critical information for future drug development