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USC team reveals structure of APOBEC family protein

Researchers at the University of Southern California have provided the first 3-D view of a protein from an enzyme family that, through its ability to mutate genes, can both help and hinder human health.

Reporting in the Dec. 24 online edition of Nature, a USC team led by Xiaojiang Chen revealed the "unusual" crystal structure of the Apo2 enzyme.

"This three-dimensional structure offers the first mechanistic analysis of any of the APOBEC enzymes at the molecular level. These proteins are important for understanding a number of critical biological processes, such as the generation of high-affinity antibodies in response to a virus or other infection," said Chen, the study's senior author and a professor of biological sciences and chemistry in USC College.

A structural biologist, Chen has produced the first x-ray crystal structures of a number of proteins important in viruses, cancer and immunity.

In one sense, the APOBEC proteins are classic saboteurs -- they all can introduce mutations into strands of DNA or RNA. Known as deaminases, APOBEC proteins catalyze a chemical reaction that changes the "C" (cytidine) of the genetic code into a "U" or (uracil). Even a one-letter change in the code can lead to a change or loss of function in an encoded protein.

Looked at from a different perspective, however, the enzyme family plays a decidedly protective role in the cell. One notable family member, the AID protein, generates the genetic diversity required for the body to produce hundreds of billions of different antibodies, each capable of targeting a specific disease-causing agent. Others have been shown to disarm viruses like HIV and hepatitis B.

Uncontrolled, of course, the APOBEC proteins could create havoc in a cell. But normally, under the cell's tight regulation, "these are the good guys," Chen said.

When Courtney Prochnow, a graduate student in Chen's lab, first revealed the atomic structure o
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Contact: Eva Emerson
eemerson@usc.edu
310-871-7638
University of Southern California
24-Dec-2006


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