STRUCTURAL STUDIES OF YEAST EXOCYTOSIS

这个子项目是众多研究子项目之一

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. Our lab is investigating the structural basis for cellular signaling using protein X-ray crystallography. One set of projects involve the Rab family of small GTPases, which orchestrate the trafficking of vesicular cargo in eukaryotic cells. Rabs have a conserved three-dimensional fold in their active (GTP) state, yet recognize a distinct subset of effector proteins to mediate their biological effects. Unlike Rabs, effector proteins are diverse in size and composition. We have determined the crystal structures of several Rab-effector complexes to gain insight into specificity and subsequent biological function. The seemingly contradictory properties of specificity and promiscuity - each Rab binds to several unrelated effectors  are being understood in light of emerging structural data. A second set of projects involve the structural basis for poxvirus antagonism of innate immunity. During infection, viral proteins interact with their cellular targets to suppress the immune response and favour viral replication. We have determined the crystal structure of protein K7 in complex with a fragment of its target, human RNA helicase DDX3. The structure reveals the molecular basis for specificity and suggests a mechanism for viral suppression of a key step in the interferon-¿ activation pathway. Similarly, work is continuing toward structural elucidation of other complexes of viral proteins and their cellular targets. Overall, our work in determining the 3-dimensional structures of cellular signaling complexes may lead to the development of novel drugs that modulate key pathways in infectious diseases.