Senior Honors Projects, 2010-2019

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Date of Graduation

Spring 2015

Document Type


Degree Name

Bachelor of Science (BS)


Department of Chemistry and Biochemistry


Nathan T. Wright


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.



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