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Date of Award
Bachelor of Science (BS)
Department of Chemistry and Biochemistry
Obscurin (720-900 kD) is a giant sarcomeric signaling protein that is the only known link
between the cytoskeleton and the surrounding membrane structure. Mutations to obscurin
and to obscurin binding partners have been linked to human muscle diseases such as
hypertrophic cardiomyopathies and muscular dystrophy. These diseases likely occur due
to the abrogation of specific molecular interactions necessary for suitable function. To
more fully understand how specific mutations lead to disease, here we solve the highresolution
structure of obscurin Ig58. The literature shows that an Arg8Gln mutation to
the Ig58 domain of obscurin is associated with hypertrophic cardiomyopathy (HCM).
Chemical shift changes of this mutation and MD simulations suggest that this mutation
disrupts a large charge-charge surface of Ig58, perturbing the titin-binding interface.
Oehler, Matthew C., "Structural studies of the Ig58 domain of the giant muscle protein obscurin" (2015). Senior Honors Projects, 2010-current. 49.