Crystal Structure of the APOBEC3G Catalytic Domain Reveals Potential Oligomerization Interfaces

Shivender M D Shandilya, Madhavi N L Nalam, Ellen A. Nalivaika, Phillip J. Gross, Johnathan C. Valesano, Keisuke Shindo, Ming Li, Mary Munson, William E. Royer, Elena Harjes, Takahide Kono, Hiroshi Matsuo, Reuben Harris, Mohan Somasundaran, Celia A. Schiffer

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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 Å. This structure corroborates features previously observed in nuclear magnetic resonance (NMR) studies, a bulge in the second β strand and a lengthening of the second α 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.

Original languageEnglish (US)
Pages (from-to)28-38
Number of pages11
JournalStructure
Volume18
Issue number1
DOIs
StatePublished - Jan 13 2010

Keywords

  • DNA
  • PROTEINS

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    Shandilya, S. M. D., Nalam, M. N. L., Nalivaika, E. A., Gross, P. J., Valesano, J. C., Shindo, K., Li, M., Munson, M., Royer, W. E., Harjes, E., Kono, T., Matsuo, H., Harris, R., Somasundaran, M., & Schiffer, C. A. (2010). Crystal Structure of the APOBEC3G Catalytic Domain Reveals Potential Oligomerization Interfaces. Structure, 18(1), 28-38. https://doi.org/10.1016/j.str.2009.10.016