2MZZ

NMR structure of APOBEC3G NTD variant, sNTD

Summary for 2MZZ

• Entry DOI: 10.2210/pdb2mzz/pdb
• NMR Information: BMRB: 25509
• Descriptor: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G variant, ZINC ION (2 entities in total)
• Functional Keywords: vif-binding domain, hydrolase, antiviral protein
• Biological source: artificial gene
• Total number of polymer chains: 1
• Total formula weight: 21381.46

Authors

Kouno, T.,Luengas, E.M.,Shigematu, M.,Shandilya, S.M.D.,Zhang, J.,Chen, L.,Hara, M.,Schiffer, C.A.,Harris, R.S.,Matsuo, H. (deposition date: 2015-02-28, release date: 2015-05-13, Last modification date: 2024-05-15)

Primary citation

Kouno, T.,Luengas, E.M.,Shigematsu, M.,Shandilya, S.M.,Zhang, J.,Chen, L.,Hara, M.,Schiffer, C.A.,Harris, R.S.,Matsuo, H.
Structure of the Vif-binding domain of the antiviral enzyme APOBEC3G.
Nat.Struct.Mol.Biol., 22:485-491, 2015

PubMed Abstract: 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 α1-β1, β2-α2 and β4-α4 loops. This structure sheds new light on the Vif-A3G interaction and provides critical information for future drug development.

PubMed: 25984970
DOI: 10.1038/nsmb.3033

Experimental method

SOLUTION NMR