Development of Solid State NMR Methods for the Structural Characterization of Membrane Proteins: Applications to Understand Multiple Sclerosis

Cosman, M ; Tran, A T ; Ulloa, J ; Maxwell, R S

Lawrence Livermore National Laboratory

关键词: Antibodies;    Diseases;    X-Ray Diffraction;    Fibers;    Myelin;   

DOI  :  10.2172/15007469
RP-ID  :  UCRL-ID-151943
RP-ID  :  W-7405-ENG-48
RP-ID  :  15007469

美国|英语

来源: UNT Digital Library

【 摘 要 】

Multiple sclerosis (MS) is a relapsing-remitting disorder of the central nervous system that results in the loss of the myelin sheaths insulating nerve fibers (axons). Strong evidence suggests that MS is an autoimmune disease mediated by T-cell and antibody responses against myelin antigens. Myelin oligodendrocyte glycoprotein (MOG) is a 26 kD to 28 kD an integral membrane protein of the central nervous system implicated as a target for autoaggressive antibodies in MS. To date, the conformation of MOG in association with the myelin membrane is unknown and the exact nature of the interactions between this protein and disease-inducing immune responses have not been determined. Since membrane associated proteins are typically characterized by decreased correlation times, solution state NMR methodologies are often impracticable. Membrane proteins are also often difficult to crystallize for X-ray diffraction studies, Consequently, there is an urgent need to develop new structure characterization tools for this important class of biomolecules. The research described here overviews the initial stages of our effort to develop an integrated, NMR based approach to structural studies of MOG over the many structural domains it is postulated to posses. The structural knowledge gained about this important MS antigen in its native environment will contribute significantly to our understanding of its function in vivo. This project will also aid in the development of therapeutics to inhibit the antigedantibody interaction and thus prevent demyelination in MS patients.