WILLIAM WEIS PRT TIME

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This program aims to determine the structures of proteins involved in cell membrane targeting, adhesion and signaling processes, in order to establish the mechanism and specificity of their interactions. There are three principal areas under investigation, all of which with crystals that require synchrotron radiation. 1. Cell-surface carbohydrate recognition in the immune system, focusing on serum Mannose-binding Proteins and how they trigger complement-mediated cell lysis, and DC-SIGN, an adhesion molecule that mediates activation of T cells by antigen-presenting cells, and which also serves to capture HIV and deliver it to T cells. 2. Architecture and assembly of intercellular junctions, studying the interactions of the proteins that link cadherin cell adhesion molecules to the cytoskeleton. The adherens junction protein beta-catenin is also an essential component of the Wnt signaling pathway, and its interactions with other Wnt pathway components are also being studied. 3. Proteins responsible for specific docking and fusion of intracellular vesicles with target membranes.