Elucidating the Intermolecular Interfaces of APOBEC3's

描述（由申请人提供）：APOBEC 3（A3 G、A3 F和可能的A3 H）是细胞DNA胞嘧啶脱氨酶，其是关键的先天性抗病毒剂，特别是响应HIV-1。虽然这些重要酶的催化结构域的结构开始被阐明，其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。在这项提案中，我们使用晶体学，分子建模，量热法，质谱和病毒研究的组合来表征各种APOBEC 3的结构域，无论是在其结构域内的分子内和分子间与HIV-1 Vif的相互作用。 公共卫生相关性：当艾滋病毒感染人体时，许多分子试图阻止病毒传播。一个这样的蛋白质家族被称为APOBEC 3。这些蛋白质试图改变病毒的RNA，使病毒的传染性降低。我们正在使用分子生物物理技术，以原子细节来可视化这些相互作用，以便它们最终能够成为药物治疗的靶点。

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.