Department of Chemistry
800 22nd street, NW | SEH 4000
Washington, DC 20052
Phone: (202) 994-6121 Fax: (202) 994-5873
E-mail: [email protected]
Website: http://chemistry.columbian.gwu.edu
Department of Chemistry Seminar
“Understanding the Mechanism of Function of MID1:
Insights into the Cause of X-linked Opitz Syndrome”
Human MID1 is a protein required for proper development of the midline during embryogenesis.
Loss of function mutations of MID1 are associated with X-linked Opitz G/BB Syndrome
(XLOS), which is characterized by wide-spaced eyes, cleft lip/palate, and defects in the brain,
heart and genitalia. Our lab has shown that MID1 catalyzes the ubiquitin modification of microtubule-associated protein phosphatase 2A and alpha4, marking them for cellular degradation.
PP2A and alpha4 are critical for routine cellular functions that include metabolism, cell-cycle
progression, transformation, cell death, and cell-cell communication. Increase amounts of these
proteins are observed with MID1 mutations.
My research focuses on characterizing the mechanisms of function of MID1 and identifying the
effects of a number of XLOS-observed mutations on structure, function and the targeting of its
substrates. In addition, we have confirmed that MID1 directly associates with the microtubules
and that its COS domain contributes to this interaction. As its role in directing the ubiquitination
of PP2A and alpha4, MID1’s B-box1 functions as an E3 ligase. We have engineered through
mutations the B-box1 domain to modify its activity and substrate recognition, allowing us to
understand its evolutionary role as an E3 ligase within MID1 and in general, how E3 ligases
function.
BIO
Katharine Wright received her B.S. in Chemistry from the University of Scranton. She performed undergraduate research in which she
analyzed and compared counterfeit vs. genuine pharmaceutical products. She joined the laboratory of Dr. Michael Massiah, in which her
research interests have shifted to biochemical characterization of protein function that includes enzymatic activities, mechanism and protein
engineering. She also uses multi-dimensional NMR to characterize the structure and function of proteins.
Katherine Wright
Graduate Student - Massiah Group
Department of Chemistry
George Washington University
Washington, DC 20052
Friday, February 24, 2017
SEH B1220
2:00 - 3:00 PM
Refreshments will be served at 1:45 PM