STRUCTURAL BIOL OF CELL SURFACE RECEPTORS RELEVANT TO HUMAN HEALTH & DIS: HIV

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我的实验室正在研究与人类健康和疾病相关的受体/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还没有被很好地理解。然而，细胞表面受体的激活是基本的每一个重要的生理功能。通过对蛋白质-蛋白质复合物的晶体学研究，我们在理解蛋白质之间的分子识别方面取得了进展。然而，激活信号在受体结合后的后续转导的分子基础，即使是最深入研究的受体系统，在很大程度上仍然是推测性的。解释激活信号产生的模型来源于对细胞外和细胞内受体结构域的结构分析，这与功能数据相一致。我的实验室正在努力解决的一般问题是，受体对配体的细胞外接合如何在结构上与细胞内信号级联的激活耦合。因此，我的实验室正试图对来自许多不同系统的受体及其配体的复合物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. 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.