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

DE200415007469

Publication Date	2003
Personal Author	Cosman, M.; Tran, A. T.; Ulloa, J.; Maxwell, R. S.
Page Count	38
Abstract	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 dlsease-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 posess. 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.
Keywords	Multiple sclerosis Nervous system disorders Central nervous system Nuclear magnetic resonance Autoimmune disease Myelin Axons Nerve fibers T-cells Antibodies Interactions Proteins Solid state Spectroscopy Multiple sclerosis (MS) Myelinoligodendrocyte glycoprotein (MOG) Myelin membrane Nuclear Magnetic Resonance (NMR) spectroscopy
Source Agency	Technical Information Center Oak Ridge Tennessee
Corporate Authors	Lawrence Livermore National Lab., CA.; Department of Energy, Washington, DC.
Supplemental Notes	Sponsored by Department of Energy, Washington, DC.
Document Type	Technical Report
NTIS Issue Number	200424

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

Development of Solid State NMR Methods for the Structural Characterisation of Membrane Proteins: Applications to Understand Multiple Sclerosis.
DE200415007469

Publication Date	2003
Personal Author	Cosman, M.; Tran, A. T.; Ulloa, J.; Maxwell, R. S.
Page Count	38
Abstract	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 dlsease-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 posess. 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.
Keywords	Multiple sclerosis Nervous system disorders Central nervous system Nuclear magnetic resonance Autoimmune disease Myelin Axons Nerve fibers T-cells Antibodies Interactions Proteins Solid state Spectroscopy Multiple sclerosis (MS) Myelinoligodendrocyte glycoprotein (MOG) Myelin membrane Nuclear Magnetic Resonance (NMR) spectroscopy
Source Agency	Technical Information Center Oak Ridge Tennessee
Corporate Authors	Lawrence Livermore National Lab., CA.; Department of Energy, Washington, DC.
Supplemental Notes	Sponsored by Department of Energy, Washington, DC.
Document Type	Technical Report
NTIS Issue Number	200424