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

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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.