Title

Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces.

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

2010-01-13

Document Type

Article

Subjects

Cytidine Deaminase; Protein Conformation; HIV-1; Nuclear Magnetic Resonance, Biomolecular

Disciplines

Biochemistry, Biophysics, and Structural Biology | Pharmacology, Toxicology and Environmental Health

Abstract

APOBEC3G is a DNA cytidine deaminase that has antiviral activity against HIV-1 and other pathogenic viruses. In this study the crystal structure of the catalytically active C-terminal domain was determined to 2.25 A. This structure corroborates features previously observed in nuclear magnetic resonance (NMR) studies, a bulge in the second beta strand and a lengthening of the second alpha helix. Oligomerization is postulated to be critical for the function of APOBEC3G. In this structure, four extensive intermolecular interfaces are observed, suggesting potential models for APOBEC3G oligomerization. The structural and functional significance of these interfaces was probed by solution NMR and disruptive variants were designed and tested for DNA deaminase and anti-HIV activities. The variant designed to disrupt the most extensive interface lost both activities. NMR solution data provides evidence that another interface, which coordinates a novel zinc site, also exists. Thus, the observed crystallographic interfaces of APOBEC3G may be important for both oligomerization and function.

Source

Structure. 2010 Jan 13;18(1):28-38.

Journal/Book/Conference Title

Structure (London, England)

Related Resources

Link to article in PubMed

PubMed ID

20152150

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