NMR structure of APOBEC3G NTD variant, sNTDNMR structure of APOBEC3G NTD variant, sNTD

Structural highlights

2mzz is a 1 chain structure with sequence from Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G.,Kouno T, Luengas EM, Shigematsu M, Shandilya SM, Zhang J, Chen L, Hara M, Schiffer CA, Harris RS, Matsuo H Nat Struct Mol Biol. 2015 May 18. doi: 10.1038/nsmb.3033. PMID:25984970[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Kouno T, Luengas EM, Shigematsu M, Shandilya SM, Zhang J, Chen L, Hara M, Schiffer CA, Harris RS, Matsuo H. Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G. Nat Struct Mol Biol. 2015 May 18. doi: 10.1038/nsmb.3033. PMID:25984970 doi:http://dx.doi.org/10.1038/nsmb.3033
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