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You searched for +publisher:"University of Illinois – Chicago" +contributor:("Kobayashi, Tomoyoshi"). Showing records 1 – 3 of 3 total matches.

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University of Illinois – Chicago

1. Genchev, Georgi Z. Computational Studies of Mechanical Signal Transduction in Proteins.

Degree: 2014, University of Illinois – Chicago

Cellular signaling is a system of complex interplay of communications that guides cellular processes and coordinates cell behavior. In this dissertation, united by three main themes, investigations of mechanisms of mechanical signal transduction in proteins are presented. The first theme focuses on chemical to mechanical signal transduction. Using molecular dynamics simulations, aspects of thin filament calcium-induced regulation are investigated. The calcium-dependent behavior of skeletal troponin, and key conformational events subsequent to calcium expulsion from troponin C regulatory sites are described. Dynamics of cardiac troponin C, and details of residue coordination leading to calcium binding in the regulatory site are elucidated. These findings are incorporated into a model integrating the calcium dependent behavior of troponin to its ability to interact with actin and regulate muscle contraction. The second theme focuses on steered molecular dynamics (SMD) investigations of force induced mechanical unfolding of slipknot proteins. Unfolding of slipknot AFV3-109 occurs via either two-state, or three-state process involving the formation of a stable intermediate state. The results demonstrate a mechanical unfolding pathway bifurcation and potential gearbox mechanism with non similar responses to pulling force that may enable differential mechanical signal transduction. The third theme focuses on two aspects of mechanical proteins stabilization to mechanical unfolding - the solvent environment effect and neighboring beta strands effect. The solvent environment plays an integral role in cellular processes. SMD unfolding of I27 and solvent substitution were combined to reveal that solvent environment modulates the force resistance of I27. During unfolding, solvent molecules interact with I27's force bearing patch, in solvent molecule geometry-dependent mode multiplicity. Protein topology and pulling geometry play important roles in determining protein mechanical stability. The critical importance of neighboring beta strands stabilization effect is explored. The proteins Top7 and barstar have similar force-bearing topology but different mechanical stability. SMD simulations of barstar reveal that barstar unfolds by beta strand peeling whereas Top7, which has two additional beta strands in its force bearing patch unfolds via substructure-sliding. This neighboring beta strands stabilization effect may be a general mechanism in protein mechanics and de-novo design guideline for mechanically stable proteins with novel topology. Advisors/Committee Members: Lu, Hui (advisor), Ansari, Anjum (committee member), Stroscio, Michael (committee member), Kobayashi, Tomoyoshi (committee member).

Subjects/Keywords: troponin; titin; slipknot; thin filament; mechanotransduction; signaling; force; molecular dynamics; steered molecular dynamics; bioinformatics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Genchev, G. Z. (2014). Computational Studies of Mechanical Signal Transduction in Proteins. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/18893

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Genchev, Georgi Z. “Computational Studies of Mechanical Signal Transduction in Proteins.” 2014. Thesis, University of Illinois – Chicago. Accessed September 19, 2020. http://hdl.handle.net/10027/18893.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Genchev, Georgi Z. “Computational Studies of Mechanical Signal Transduction in Proteins.” 2014. Web. 19 Sep 2020.

Vancouver:

Genchev GZ. Computational Studies of Mechanical Signal Transduction in Proteins. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2020 Sep 19]. Available from: http://hdl.handle.net/10027/18893.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Genchev GZ. Computational Studies of Mechanical Signal Transduction in Proteins. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/18893

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of Illinois – Chicago

2. Mouannes, Julie J. Troponin I Inhibitory Region’s Role in Cardiac Muscle Regulation and Troponin Structural Dynamics.

Degree: 2014, University of Illinois – Chicago

To maintain cardiovascular homeostasis, the heart adapts to circulatory needs and/or stress in a greatly malleable process involving specific regulatory mechanisms. Troponin plays a crucial role in such regulation, by acting as the protein on-off switch of the cardiac muscle contractile apparatus. Within troponin, troponin I (TnI) is considered to be the critical troponin subunit for switching off the heart in the absence of Ca2+, in significant part via the action of a small portion of TnI termed the inhibitory peptide region. This thesis examines the role of the inhibitory region of TnI in cardiac muscle regulation, as well as the effects of the inhibitory region on overall troponin dynamics both locally and at a distance. The first part of this thesis explains how troponin's inhibitory effects have previously been shown to be mimicked by this 12-residue TnI peptide, termed the inhibitory peptide. Mutagenesis of this segment within the whole troponin context can be used to investigate how the inhibitory peptide region alters the thin filament to affect or effect regulation. Accordingly, we describe the functional properties of troponins containing mutations within the inhibitory peptide sequence. Smaller or larger portions were replaced with Gly-Ala linkers. The results show that the mutations impaired Ca2+-mediated regulation of both ATPase rates and myosin binding to the thin filament. The regulatory impairment was considerable, supporting an important role for the inhibitory peptide region. On the other hand, even for thin filaments with complete replacement of the inhibitory peptide region, Ca2+ addition caused a cooperative increase in myosin-thin filament ATPase activity. This points to the co-importance of other parts of troponin as mediators of inhibition and activation generally, and of cooperative regulation specifically. The relationship of these findings to the overall regulatory mechanism is discussed. In the second part of the thesis, we use hydrogen deuterium exchange coupled with mass spectrometry (HDX-MS) to study the dynamic properties of troponin composed of cTnT, cTnI with the complete inhibitory region replaced with a flexible linker and cTnC with mutational inactivation of site II Ca2+ binding. Additionally, we study the dynamics of a troponin complex similar to the one above but with wild type TnC instead. This allowed the determination of the effects of the inhibitory region on troponin dynamics both in the presence and absence of Ca2+. HDX allows for the mapping, in detail, quantitatively, of the dynamic properties of each part of cardiac troponin. H-D exchange rates in folded proteins tend to track with local folding instability. Therefore, measurements of local rates of exchange across a protein provide quantitative dynamic information on various distinct regions of that protein. We propose that, in the absence of Ca2+ bound to regulatory site II of TnC, the Ip region has unexpected importance for stabilizing intra-troponin interactions relatively distant from the Ip region itself.… Advisors/Committee Members: Solaro, R. John (advisor), Tobacman, Larry S. (committee member), Lewandowski, E. Douglas (committee member), Kobayashi, Tomoyoshi (committee member), Colley, Karen (committee member).

Subjects/Keywords: Troponin; Troponin I; Muscle regulation; Hydrogen Deuterium Exchange

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Mouannes, J. J. (2014). Troponin I Inhibitory Region’s Role in Cardiac Muscle Regulation and Troponin Structural Dynamics. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/18874

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Mouannes, Julie J. “Troponin I Inhibitory Region’s Role in Cardiac Muscle Regulation and Troponin Structural Dynamics.” 2014. Thesis, University of Illinois – Chicago. Accessed September 19, 2020. http://hdl.handle.net/10027/18874.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Mouannes, Julie J. “Troponin I Inhibitory Region’s Role in Cardiac Muscle Regulation and Troponin Structural Dynamics.” 2014. Web. 19 Sep 2020.

Vancouver:

Mouannes JJ. Troponin I Inhibitory Region’s Role in Cardiac Muscle Regulation and Troponin Structural Dynamics. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2020 Sep 19]. Available from: http://hdl.handle.net/10027/18874.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mouannes JJ. Troponin I Inhibitory Region’s Role in Cardiac Muscle Regulation and Troponin Structural Dynamics. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/18874

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Yar, Sumeyye. Cardiac Tropomyosin D137L Mutation Decreases Structural Flexibility to Cause Systolic Dysfunction.

Degree: 2014, University of Illinois – Chicago

The work presented in this thesis addresses major gaps in our understanding of how thin filament control mechanisms translate to regulate cardiac function. Here we focus on α-tropomyosin (α-TM) as a nodal point in control of the thin filament state. α-TM carries a conserved, charged residue (Asp137) located in the hydrophobic core of its coiled-coil structure.This is distinct to the α-TM coiled-coil in that the residue is found at a position typically occupied by a hydrophobic residue.Via substituting this Asp137 with a more expected canonical Leu, it was previously shown that Asp137 destabilizes a region in the middle of α-TM, inducing a more flexible local region that is important for modulating the cooperative activation of the thin filaments. In the first part of this study, we extend these earlier findings and demonstrate that D137L mutation decreases global flexibility of α-TM and cause long-range structural rearrangements. Although much has been inferred with regard to the role of α-TM flexibility in sarcomeric control mechanisms, its relative significance in vivo is unclear. Therefore, in the second part of this study, we investigate implications of α-TM flexibility on in situ cardiac function in a novel transgenic mouse model expressing α-TM-D137L in the heart. To our knowledge, our findings are the first to demonstrate that the marked decrease in TM’s structural flexibility due to substitution of Asp 137 with Leu depresses systolic parameters of cardiac contraction and ultimately leads to a phenotype similar to dilated cardiomyopathy. At the sarcomere level, our results show that expression of α-TM-D137L in TG mouse hearts affect Ca2+ dependent activation of thin filaments while causing no change in the strongly bound cross-bridge dependent activation. Therefore we propose a mechanism that the decreased flexibility of α-TM-D137L impedes Ca2+ dependent relocation of α-TM on actin resulting in a delay in time sensitive activation and relaxation processes in cardiac muscle, which eventually leads to systolic dysfunction in TG mouse hearts. Collectively, this work sheds light on a functionally important structural characteristic of α-TM and suggests a possible association between flexibility of α-TM and cardiac disorders. Advisors/Committee Members: Solaro, Ross J. (advisor), Gaponenko, Vadim (committee member), Colley, Karen J. (committee member), Caffrey, Michael (committee member), Raychaudhuri, Pradip (committee member), Kobayashi, Tomoyoshi (committee member).

Subjects/Keywords: Cardiac muscle; Flexibility; Tropomyosin; Thin filament; Cardiovascular disease; transgenic mouse model; tropomyosin flexibility; troponin; sarcomere; D137L, Asp137

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Yar, S. (2014). Cardiac Tropomyosin D137L Mutation Decreases Structural Flexibility to Cause Systolic Dysfunction. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/11257

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Yar, Sumeyye. “Cardiac Tropomyosin D137L Mutation Decreases Structural Flexibility to Cause Systolic Dysfunction.” 2014. Thesis, University of Illinois – Chicago. Accessed September 19, 2020. http://hdl.handle.net/10027/11257.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Yar, Sumeyye. “Cardiac Tropomyosin D137L Mutation Decreases Structural Flexibility to Cause Systolic Dysfunction.” 2014. Web. 19 Sep 2020.

Vancouver:

Yar S. Cardiac Tropomyosin D137L Mutation Decreases Structural Flexibility to Cause Systolic Dysfunction. [Internet] [Thesis]. University of Illinois – Chicago; 2014. [cited 2020 Sep 19]. Available from: http://hdl.handle.net/10027/11257.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yar S. Cardiac Tropomyosin D137L Mutation Decreases Structural Flexibility to Cause Systolic Dysfunction. [Thesis]. University of Illinois – Chicago; 2014. Available from: http://hdl.handle.net/10027/11257

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.