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Research | Core Facilities | Patient Studies | Tech Transfer | Seminars | Intranet | Careers | Search | Contact Us | Ways To Give HOME |
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Research Interests Interactions between Rab5 and its upstream regulators and downstream effectors are essential for early endosome fusion. Many human diseases, including some neuronal degeneration diseases, are directly related to the dysfunction of Rab5. The structural bases of Rab5-centered network interaction remains to be fully elucidated. We have determined the crystal structures of a number of protein complexes involved in these interactions. For example, the complex crystal structure of Rab5 and its effector Rabaptin5 shows an exciting snapshot of the activation stage of early endosome fusion. Our GDP-Rab5 complex crystal structure documents two unusual conformations of this GTPase molecular switch that may have important implications in understanding the molecular switching mechanisms of the Rab family. The crystal structure of a Rab5 activator, Rabex5 Vps9 domain, suggests a chaperone role to convert Rab5 through multiple conformations during the activation process. Our GGA-Rabaptin5 complex crystal structure reveals potential new links between vesicle assembly and fusion regulation. Currently, we are studying the complex structure between Rabex5 and Rabaptin5 and the functional role of this complex in Rab5 activation. Our preliminary data suggest a scaffold role for Rabaptin5 to coordinate numerous Rab5 interacting proteins. The long-term goal of this project is to understand the structural bases of pathological effects of Rab5 malfunction in endocytosis regulation. We are also interested in the interaction between the major anthrax toxins and host receptors, which is critical for the internalization and toxicity of the anthrax toxin which consists of three components, namely protective antigen, lethal factor and edema factor secreted by Bacillus anthracis. Our approach is to use X-ray crystallography to study the interactions between the protective antigen and the receptor and between the lethal factor and protective antigen thus to develop novel strategies to block entry of the anthrax toxin into the host cell. We also study the structural aspects of the thrombolytic-fibrinolytic
system. This work has revealed the structural bases of plasminogen activation mechanism by
streptokinase, a plasminogen activator secreted by hemorrhage strain of streptococcus, which is
widely used in the treatment of acute myocardial infarction. We are expanding our study to other
bacterial plasminogen activators, and new techniques are being explored to complement the
crystallography method to study the similarities and differences among the molecular mechanisms
employed by these activators. Joined OMRF Scientific Staff in 1995. Mailing Address
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