STRUCT BIOLOGY OF CELL SURFACE RECEPTORS RELEVANT TO HUMAN HEALTH & DISEASE: HIV

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我的实验室正在研究与人类健康和艾滋病等疾病相关的受体/配体系统中细胞表面受体识别和激活的结构方面。信息从细胞外部传递到细胞内部的分子机制仍然不是很清楚。然而，细胞表面受体的激活是几乎所有重要生理功能的基础。通过蛋白质-蛋白质复合体的结晶学研究，我们在理解蛋白质之间的分子识别方面取得了进展。然而，即使是最深入研究的受体系统，在受体参与时，随后激活信号转导的分子基础在很大程度上仍然是推测的。解释激活信号产生的模型是通过对受体胞外和胞内结构域的结构分析得出的，这些结构分析已经与功能数据相一致。我的实验室正在努力解决的一般问题是，受体对细胞外配体的参与如何在结构上与细胞内信号级联的激活相联系。因此，我的实验室正在尝试对来自许多不同系统的受体及其配体形成的络合物的光谱进行晶体结构测定。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. My laboratory is investigating structural aspects of cell-surface receptor recognition and activation, in receptor/ligand systems relevant to human health and disease, such as AIDS. The molecular mechanisms by which information is communicated from the outside to the inside of a cell are still not well understood. Yet, cell-surface receptor activation is fundamental to essentially every vital physiological function. We are making progress in understanding molecular recognition between proteins through crystallographic studies of protein-protein complexes. However, the molecular bases for the subsequent transduction of an activation signal, upon receptor engagement, remains largely speculative for even the most intensively studied receptor systems. Models to explain the generation of an activation signal have been derived from structural analysis of receptor extracellular and intracellular domains which have been reconciled with functional data. The general question my laboratory is endeavoring to address is how the extracellular engagement of a ligand by a receptor is structurally coupled to the activation of intracellular signaling cascades. As such, my laboratory is attempting to carry out crystal structure determinations of a spectrum of receptors in complex with their ligands from a number of different systems.