Matthews
C. Robert Matthews, Ph.D.
Chair and Arthur F. and Helen P. Koskinas Professor of
Biochemistry and Molecular Pharmacology
University of Massachusetts Medical School
364 Plantation Street
Worcester, MA 01605
(508) 856-2251
c.robert.matthews@umassmed.edu
Faculty page:  http://profiles.umassmed.edu/profiles/ProfileDetails.aspx?From=SE&Person=603

Our interest in amyotrophic lateral sclerosis revolves around the molecular basis by which numerous point mutations in superoxide dismutase (SOD1) lead to aggregation and motor neuron death. We employ a host of biophysical approaches to understand the perturbations in the populations of monomeric and dimeric forms of SOD1induced by amino acid replacements. Aggregation reactions are acutely sensitive to these populations, and our studies are expected to highlight candidates for nucleation events. Kinetic studies focus on the lifetimes of various species on the folding reaction coordinate, with the expectation that increased lifetimes along with enhanced populations increase the propensity for aggregation. Structural studies on protein aggregates created in vitro are intended to reveal the segments of SOD1 that drive the large scale association reactions responsible for aggregation.

References:

Svensson, A.K., Bilsel, O., Kondrashkina, E., Zitzewitz, J.A., Matthews C.R., “Mapping the Folding Free Energy Surface for Metal-free Human Cu,Zn Superoxide Dismutase,” J. Mol. Biol., 364, 1084-1102 (2006).

Kayatekin, C.; Zitzewitz, J.A.; Matthews, C.R. “Zinc Binding Modulates the Entire Folding Free Energy Surface of human Cu,Zn Superoxide Dismutase,” J. Mol. Biol., 384, 540-555 (2008). PMC2756654

Kayatekin, C.; Zitzewitz, J.A.; Matthews, C.R.“Disulfide-reduced ALS-Variants of Cu,Zn Superoxide Dismutase are Partially Denatured” J. Mol. Biol., 398, 320-331 (2010). PMCID in process.

Svensson, A.K.E.; Bilsel, O.; Kayatekin, C.; Adefusika, J.A.; Zitzewitz, J.A.; Matthews, C.R. “Metal-free ALS-Variants of Dimeric Human Cu, Zn-Superoxide Dismutase have Enhanced Populations of Monomeric Species,” PLoS ONE, 5, e10064 (2010). 

 

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