Resource type
Thesis type
(Thesis) M.Sc.
Date created
2014-05-29
Authors/Contributors
Author: Lotfalisalmasi, Bairam
Abstract
Human cardiac troponin C (HcTnC), the regulatory calcium-binding component of the troponin complex, is responsible for the regulation of cardiac muscle contraction in response to varying cytosolic calcium levels. Mutations that are shown to increase the cTnC Ca2+ affinity are hypothesized to induce hypertrophic cardiomyopathies (HCM). Several mutations in HcTnC have been selected that are associated with HCM. These mutations include A8V, L29Q, C84Y, E134D, and D145E. The structural effects of these mutations have been modeled through equilibrium molecular dynamics and their functional and structural impacts have been assessed. In each mutant that was analyzed, the equilibrated structures have shown notable deviations from wild-type in the regions known to be cardiac troponin I (cTnI) interaction sites. There were differences in the conformation dynamics of site II and cTnC/cTnI interaction sites. We anticipate these correlations may contribute to Ca2+ affinity either directly or indirectly through cTnI association.
Document
Identifier
etd8419
Copyright statement
Copyright is held by the author.
Scholarly level
Supervisor or Senior Supervisor
Thesis advisor: Tibbits, Glen
Member of collection
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