2x83

Evolutionary basis of HIV restriction by the antiretroviral TRIMCyp

spinqualitylabelsall models 2x83, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2x83 is a 4 chain structure with sequence from Human immunodeficiency virus type 1 lw12.3 isolate and Macaca fascicularis. The July 2013 RCSB PDB Molecule of the Month feature on HIV Capsid by David Goodsell is 10.2210/rcsb_pdb/mom_2013_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E9MJX7_9HIV1 Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.,Ylinen LM, Price AJ, Rasaiyaah J, Hue S, Rose NJ, Marzetta F, James LC, Towers GJ PLoS Pathog. 2010 Aug 19;6(8). pii: e1001062. PMID:20808866 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures

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