dc.contributor.advisor | Conover, Gloria M | |
dc.creator | Jacobs, Krystyna M | |
dc.date.accessioned | 2013-06-04T16:10:16Z | |
dc.date.available | 2013-06-04T16:10:16Z | |
dc.date.created | 2010-05 | |
dc.date.issued | 2012-07-11 | |
dc.date.submitted | May 2010 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/ETD-TAMU-2010-05-8115 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/148748 | |
dc.description.abstract | Our research focuses on the role of intermediate proteins in human disease. Desmin, a
major intermediate filament protein in muscle cells, is organized into a central coiledcoil
alpha helical domain flanked by globular head and tail domains. Our goal is to
decipher the functional significance of the association of desmin to the giant thin
filament protein nebulin at the sarcomeric Z-discs and its relation to muscle disease.
Mutations in nebulin cause nemaline myopathy, a debilitating genetic muscle disease
that affects children and adults alike. Previous research has shown that nebulin has a
high affinity binding to desmin. However, little is known about the contribution of
lower affinity binding desmin domains to nebulin or about the involvement of this
interaction in nemaline myopathy. We hypothesize that the desmin 3-dimensional
linkage to nebulin contributes to nemaline myopathy pathology. To test our hypothesis,
we tested the binding profile of a nebulin-associated nemaline myopathy mutation to
particular desmin domains using biochemical approaches. Our ELISA and GST-pull
down assays showed that nebulin modules 160-164 bind to desmin?s central rod coil 2b and tail subdomains. Moreover, we found significantly decreased binding of the desmin
coil 2b to the nemaline myopathy Nebulin M160-164 T5681P mutant as compared to
nebulin M160-164. A 3-fold binding increase of the coil 2b was found in random
alanine nebulin M160-164 L5646A mutant as compared to nebulin nemaline-associated
nebulin M160-164 T5681P mutant, underscoring the importance of this region to the
interaction of desmin and nebulin. Taken together, our findings suggest that differences
in the binding profile of nemaline-associated nebulin mutations to desmin may
contribute to our understanding the underlying molecular mechanism responsible for this
disease. This knowledge may be significant because it may aid in devising new
treatments for nemaline myopathy patients in the future. | en |
dc.format.mimetype | application/pdf | |
dc.subject | Nebulin | en |
dc.subject | Desmin | en |
dc.subject | Nebulin M160-164 | en |
dc.subject | T5681P | en |
dc.subject | L5646A | en |
dc.subject | Nemalin Myopathy mutations | en |
dc.subject | intermediate filaments, sarcomere, striated muscle | en |
dc.title | Deciphering the Effect of Nemaline-Myopathy Nebulin Mutations on Desmin Binding | en |
dc.type | Thesis | en |
thesis.degree.department | College of Veterinary Medicine and Biomedical Sciences | en |
thesis.degree.discipline | Biomedical Sciences | en |
thesis.degree.grantor | Honors and Undergraduate Research | en |
thesis.degree.name | Bachelor of Science | en |
dc.type.material | text | en |
dc.date.updated | 2013-06-04T16:10:16Z | |