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 2017

Document Type

Thesis

Degree Name

Bachelor of Science (BS)

Department

Department of Chemistry and Biochemistry

Advisor(s)

Nathan T. Wright

Isaiah C. Sumner

Christopher E. Berndsen

Abstract

Obscurin (800-900 kDa) is a giant cytoskeletal protein important to muscle cell maintenance and organization. One of its functions is to connect distal regions within the cell. The protein architecture suggests this role; obscurin consists of dozens of individually-folded domains linked together. Given obscurin’s shape and position in the cell, it likely responds to cell motion and stretch by itself stretching and compressing. One outstanding question is how obscurin accomplishes this. Here, we begin to probe the molecular mechanism and outcomes of obscurin stretch resistance. We hypothesize that obscurin could either act like a rope, only resisting stretch when fully extended, or it could act as a spring, resisting stretch regardless of how extended it is. By studying a collection of representative obscurin domains and tandem domains, using nuclear magnetic resonance (NMR) and small angle X-ray diffraction (SAXS) techniques, we gain insight into obscurin’s shape and self-interactions. Using computational techniques, we supplement our wet lab data and gain increased understanding of how obscurin resists external force. Our data suggest that different tandem domains, with unique linker sequences (but not lengths) variably react to stretch. As all of these domains are within one obscurin molecule, these results show obscurin to be a nonuniform force resistor; different regions resist force to different magnitudes.

Included in

Biophysics Commons

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.