Elucidating the Intermolecular Interfaces of APOBEC3's

描述（由申请人提供）：APOBEC3's （A3G, A3F，可能还有A3H）是细胞DNA胞嘧啶脱氨酶，是关键的先天抗病毒药物，特别是在HIV-1反应中。虽然这些重要酶的催化结构域的结构已经开始被阐明，但它们的特异性和与其他细胞和病毒大分子的相互作用的细节仍然有待确定。在本研究中，我们结合了晶体学、分子模型、量热法、质谱法和病毒研究来表征各种APOBEC3的结构域，包括分子内结构域和分子间与HIV-1 Vif的相互作用。

DESCRIPTION (provided by applicant): The APOBEC3's (A3G, A3F and possibly A3H) are cellular DNA cytosine deaminases that are key innate anti-viral agents, particularly in response to HIV-1. Although the structures of the catalytic domains of these important enzymes are beginning to be elucidated, the details of their specificities and interactions with other cellular and viral macromolecules still remains to be determined. In this proposal we are using a combination of crystallographic, molecular modeling, calorimetry, mass spectrometry and viral studies to characterize the domains of the various APOBEC3's, both intra-molecularly within their domains and inter-molecularly with their interactions with HIV-1 Vif. PUBLIC HEALTH RELEVANCE: When HIV infects the human body, many molecules attempt to prevent the virus from spreading. One such family of proteins are called the APOBEC3's. These proteins attempt to change the viral RNA, to make the virus less infectious. We are using molecular biophysical techniques to visualize these interactions in atomic detail, so that they can eventually be targeted for drug therapy.