CRYSTAL STRUCTURE DETERMINATION OF MYELIN PROTEINS

Stanford University, Stanford CA

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Abstract

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. Myelin is the complex structure of multiple phospholipidic membranes that surrounds the axons in the nervous systems. In our laboratory we are interested in defining the atomic structure of compacted myelin. In the central nervous system myelin is formed mainly by two proteins, myelin basic protein (MBP) and proteolipid protein (PLP);at the same time, claudin-11 forms tight junctions that electrically seal the edges of the Ranvier nodules. PLP and claudin-11 are integral membrane proteins, while MBP is a cytoplasmic protein. Solving the unknown atomic structure of the three proteins by Se-Met MAD, we aim to understand the vital packing of membranes that it is compromised when the autoimmune multiple-sclerosis disease emerges. In another line of research, we are studying the structure of the tumor suppressor p53, which is mutated in 50% of all the cancer cases because its central role in the cellular response to DNA damage. We are focusing in the transcription regulation domain which structure is unknown. By phosphorylation, acetylation, methylation and ubiquitination of this domain the activity of p53 is regulated. Initially, we are trying to define its atomic structure in the absence of any modification, to later understand how the different modification affect its regulatory cycle.