Electronic Resource
Cardiac Myosin-Binding Protein C N-Terminal Dynamics: Structural Insights from Time-Resolved Fluorescence Studies
| العنوان: | Cardiac Myosin-Binding Protein C N-Terminal Dynamics: Structural Insights from Time-Resolved Fluorescence Studies |
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| المؤلفون: | Tardiff, Jil, Colson, Brett, Montfort, William, Kanassatega, Rhye-Samuel |
| بيانات النشر: | The University of Arizona. 2023 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Cardiac myosin-binding protein C (cMyBP-C) is a thick filament-associated sarcomeric protein that modulates the strength and kinetics of cardiac muscle contraction and relaxation. This function is further mediated by PKA phosphorylation of cMyBP-C in response to beta-adrenergic stimulation. cMyBP-C is localized to the C-zone on each half of the sarcomere by interactions of its C-terminal domains with titin and myosin that anchor cMyBP-C to the thick filament backbone. The N-terminal domains of cMyBP-C may extend towards the thin filament, possibly to dynamically interact with myosin-thick filaments and/or actin-thin filaments in a phosphorylation-dependent manner. However, the molecular mechanisms responsible for cMyBP-C effects on cardiac muscle structure and function in normal physiological conditions remain incompletely understood. In an added level of complexity, mutations in the gene encoding cMyBP-C, MYBPC3, represent a leading cause of hypertrophic cardiomyopathy (HCM). A majority of cMyBP-C-associated HCM mutations are C-terminal truncation mutations leading to reduced cMyBP-C incorporation in the sarcomere (i.e., haploinsufficiency). In contrast, the molecular processes by which N-terminal cMyBP-C point (i.e., missense) mutations cause HCM are largely unknown. Therefore, the purpose of this Dissertation is to advance mechanistic knowledge, at the molecular level, of how N-terminal cMyBP-C structure and function are regulated by PKA-mediated phosphorylation and HCM mutations to influence myofilament function by using cutting-edge biochemical and biophysical approaches, including site-directed spectroscopy. Chapter 1 of this Dissertation provides a background reviewing known aspects of cMyBP-C structure and function in cardiac muscle contraction as well as an overview of site-directed spectroscopic methods. Chapter 2 examines cMyBP-C’s regulatory role in weak-to-strong transitions in actin structural dynamics in response to cMyBP-C binding and its phosphoryla |
| مصطلحات الفهرس: | Electronic Dissertation, text |
| URL: | |
| الاتاحة: | Open access content. Open access content http://rightsstatements.org/vocab/InC/1.0 Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
| Other Numbers: | AZU oai:repository.arizona.edu:10150/668428 Kanassatega, Rhye-Samuel. (2023). Cardiac Myosin-Binding Protein C N-Terminal Dynamics: Structural Insights from Time-Resolved Fluorescence Studies (Doctoral dissertation, University of Arizona, Tucson, USA). 1397524024 |
| المصدر المساهم: | UNIV OF ARIZONA From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1397524024 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |