STUDIES OF THE INTERACTION OF ANNEXIN V, CALCIUM, ZINC AND PHOSPHOLIPIDS USING

点击翻译按钮获取中文摘要

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. Matrix vesicles are chondrocyte-derived microstructures found in a variety of mineralizing tissues such as growth plate and osteoarthritic cartilage. Matrix vesicles contain significant amounts of phospholipids, electrolytes and Annexin V protein. Annexin V is a calcium / zinc phospholipid-dependent binding protein that is thought to play a key role in the initiation of biomineralization. We have obtained crystal structures of Annexin V in the presence of calcium and zinc ions. However, no crystal structures showing the position of the proteins ligand, phosphatidylserine, are yet available. It is known however, that Annexin V undergoes a conformational change upon calcium-dependent acidic phospholipid binding, where a single tryptophan residue moves from a hydrophobic region within the protein to an extended position on the outer protein surface. Accordingly, I am requesting the use of Teragrid computational resources to run NAMD simulations on Annexin V, in the presence / absence of calcium, zinc, and various phospholipids and phospholipids bilayers. These studies could provide insight into the initial events involved in the mechanism of biological mineralization.