STRUCTURAL ANALYSIS OF FULL-LENGTH ANNEXIN 1 AND 2 IN COMPLEX WITH SPECIFIC LIGA

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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. Annexins 1 and 2 belong to a family of calcium- and phospholipid binding proteins of unknown function. They are structurally divided into a conserved core and a variable N-terminal domain. The core is responsible for calcium-dependent membrane binding, whereas the N-terminal domain regulates the specific function of each annexin. Annexins 1 and 2 are able to promote membrane aggregation in vitro, however the mechanism of this reaction is not known. In order to understand annexin-induced membrane aggregation, we solved the structure of full-length annexin 1 in the absence of calcium ions. This new structure indeed resulted in a hypothesis of annexin 1-induced membrane aggregation. We believe that the N-terminal domain might induce membrane aggregation after the protein is bound to a membrane in a calcium-dependent manner. Upon this binding event, the N-terminal domain that was buried in the core of the protein in the absence of calcium might become accessible and interact with a second membrane. In order to proof our hypothesis, we need to solve the structure of full-length annexin 1 in the presence of calcium. We already have crystals of annexin 1 in the presence of calcium and we would like to get higher resolution data. We also have crystals of annexin 2 in the presence and absence of calcium ions that we would like to investigate at your facility.