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003 OCoLC;

005 20161027015235.0;

006 m o d ;

007 cr unu||||||||;

008 160829s2016 ncua obm 000 0 eng d;

035 a| (Sirsi) o957491795;

035 a| (OCoLC)957491795;

049 a| EREE;

090 a| QP552.M93;

100 1 a| Johnson, Dylan James,e| author.?| UNAUTHORIZED;

245 10 a| Defining the role of the C-terminal region of troponin T by analysis of a series of truncation mutants /c| by Dylan James Johnson.;

264 1 a| [Greenville, N.C.] :b| [East Carolina University],c| 2016.;

300 a| 135 pages :b| illustrations (some color);

336 a| textb| txt2| rdacontent;

337 a| computerb| c2| rdamedia;

338 a| online resourceb| cr2| rdacarrier;

347 a| text fileb| PDFc| 3.07 MB2| rda;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| M.S.c| East Carolina Universityd| 2016.;

500 a| Presented to the faculty of the Department of Chemistry.;

500 a| Advisor: Colin Burns.;

500 a| Title from PDF t.p. (viewed September 22, 2016).;

520 3 a| Familial hypertrophic cardiomyopathy and other cardiovascular diseases result from mutations of any of the contractile proteins. Mutations within the actin binding regulatory complex of proteins, including tropomyosin (Tm) and the three subunits of the troponin (Tn) complex (TnI, TnC, and TnT), change the operation of the Ca2+ dependent 3-way switch that controls movement. The [Delta]14-TnT mutation, which is missing the last 14 residues of its C-terminus, is particularly important as it leads to hypertrophic cardiomyopathy and early sudden death. Our laboratory found that incorporation of [delta]14-TnT into the regulatory complex stabilizes the open (M) state and removes the blocked (B) state from the actin state distribution. This suggests the last fourteen residues of the C-terminus of TnT are essential in maintaining the open state and the blocked state of the thin filament. This function had not previously been attributed to TnT. Our lab aims to identify the key residues of TnT that are responsible for normal state distribution. This information will allow us to identify possible mechanisms of action of TnT and would facilitate the design of treatments of myopathies. We prepared truncation mutants of TnT that included [delta]4, [delta]6, [delta]8, [delta]10 and [delta]14. We utilized two stopped flow kinetic assays and an ATPase assay to determine the effect of these deletions on the state distributions. Each assay supported the idea that successive deletions resulted in further diminished function. We conclude that all of the fourteen residues of the TnT C-terminus contribute to a similar extent to the function.;

504 a| Includes bibliographical references.;

650 0 a| Tropomyosinsx| Analysis.=| ^A1017459;

650 0 a| Proteinsx| Analysis.=| ^A4852;

650 0 a| Heartx| Hypertrophy.=| ^A380153;

650 0 a| Cardiovascular systemx| Diseases.=| ^A7485;

650 0 a| Mutation (Biology)=| ^A2390;

653 a| troponin;

653 a| cardiomyopathy;

653 a| TnT;

700 1 a| Burns, Colin Sanderson,e| degree supervisor.=| ^A1217829;

710 2 a| East Carolina University.b| Department of Chemistry.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/5931;

949 o| wjh;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 4511338;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4511338-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 8/29/2016x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4511338-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 8/29/2016x| ETDz| HERESOURCE;

Defining the role of the C-terminal region of troponin T by analysis of a series of truncation mutants / by Dylan James Johnson.

Author/creator	Johnson, Dylan James author.
Other author	Burns, Colin Sanderson, degree supervisor.
Other author	East Carolina University. Department of Chemistry.
Format	Theses and dissertations
Publication	[Greenville, N.C.] : [East Carolina University], 2016.
Description	135 pages : illustrations (some color)
Supplemental Content	Access via ScholarShip
Subjects	Tropomyosins--Analysis. Proteins--Analysis. Heart--Hypertrophy. Cardiovascular system--Diseases. Mutation (Biology)

Summary	Familial hypertrophic cardiomyopathy and other cardiovascular diseases result from mutations of any of the contractile proteins. Mutations within the actin binding regulatory complex of proteins, including tropomyosin (Tm) and the three subunits of the troponin (Tn) complex (TnI, TnC, and TnT), change the operation of the Ca2+ dependent 3-way switch that controls movement. The [Delta]14-TnT mutation, which is missing the last 14 residues of its C-terminus, is particularly important as it leads to hypertrophic cardiomyopathy and early sudden death. Our laboratory found that incorporation of [delta]14-TnT into the regulatory complex stabilizes the open (M) state and removes the blocked (B) state from the actin state distribution. This suggests the last fourteen residues of the C-terminus of TnT are essential in maintaining the open state and the blocked state of the thin filament. This function had not previously been attributed to TnT. Our lab aims to identify the key residues of TnT that are responsible for normal state distribution. This information will allow us to identify possible mechanisms of action of TnT and would facilitate the design of treatments of myopathies. We prepared truncation mutants of TnT that included [delta]4, [delta]6, [delta]8, [delta]10 and [delta]14. We utilized two stopped flow kinetic assays and an ATPase assay to determine the effect of these deletions on the state distributions. Each assay supported the idea that successive deletions resulted in further diminished function. We conclude that all of the fourteen residues of the TnT C-terminus contribute to a similar extent to the function.
General note	Presented to the faculty of the Department of Chemistry.
General note	Advisor: Colin Burns.
General note	Title from PDF t.p. (viewed September 22, 2016).
Dissertation note	M.S. East Carolina University 2016.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Defining the role of the C-terminal region of troponin T by analysis of a series of truncation mutants / by Dylan James Johnson.

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