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001 ocn936177972;

003 OCoLC;

005 20160329120813.0;

006 m o d ;

007 cr bn|||||||||;

008 160128s2016 ncua obm 000 0 eng d;

035 a| (Sirsi) o936177972;

035 a| (OCoLC)936177972;

049 a| EREE;

090 a| QD431.25.A53;

100 1 a| Biscardi, Brianna,e| author.?| UNAUTHORIZED;

245 10 a| Investigating intra- and inter-molecular coevolution of intrinsically disordered protein, Prothymosin-[alpha] /c| by Brianna Biscardi.;

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

300 a| 80 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| 4.4Mb2| 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 S. Burns.;

520 3 a| Prothymosin-[alpha] (ProT[alpha]) is a small, highly acidic protein found in the nuclei of virtually all mammalian tissues. It belongs to a class of proteins known for their lack of a rigid three-dimensional structure called intrinsically disordered proteins (IDPs). ProT[alpha] has been shown to play essential roles in cell robustness. As an example, ProT[alpha] is involved in apoptosis, or programmed cell death by inhibiting apoptosome formation via binding Apaf1. This research focus is on detecting coevolution of ProT[alpha] and between ProT[alpha] and Apaf1 (ProT[alpha]-Apaf1 or ProT[alpha]-Apaf1 complex). Coevolution refers to correlated changes between pairs of interacting species to maintain or refine functional interaction. Coevolution can be defined at the molecular level as correlated sequence changes that occur to maintain a structural or functional interaction. Studying coevolution of ProT[alpha] and ProT[alpha]-Apaf1 may provide useful information such as structural contacts and specific residues necessary for complex formation. In this study, a pipeline for performing molecular coevolution studies was established at East Carolina University (ECU). This pipeline was used to analyze myoglobin, ProT[alpha] and ProT[alpha]-Apaf1. Myoglobin has been a target of previous coevolutionary studies and was chosen to test the robustness of the pipeline developed in this study. Most of the coevolving residues that were found in myoglobin match closely with those detected in other work. ProT[alpha] which has never been studied by way of coevolution, displays several coevolving residues involved in long range interactions or functionally important regions. These methods were also applied to ProT[alpha] -Apaf1 complex. Previous experimental studies using 1H-15N heteronuclear single quantum coherence (HSQC) NMR have revealed residues on ProT[alpha] necessary for interaction with Apaf1 however the residues on Apaf1 necessary for interaction with ProT[alpha] have not been resolved. Several residues of ProT[alpha] were found to have coevolution with Apaf1. Docking studies were performed to simulate binding between ProT[alpha] and Apaf1 at the sites detected in this study (ProT[alpha],Thr8, Thr107; Apaf1: Ser1056, Asp1096). Six orientations of ProT[alpha] and Apaf1 were run for 9 nanoseconds (ns) and in each simulation, the two proteins did not drift apart from one another. This suggests that the residues detected by coevolution in this study may play a role in the interaction between ProT[alpha] and Apaf1.;

504 a| Includes bibliographical references.;

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

650 0 a| Coevolution.=| ^A187465;

650 0 a| Myoglobin.=| ^A228031;

653 a| IDP;

653 a| Intrinsically Disordered;

653 a| Prothymosin-alpha;

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/10342/5101;

949 o| wjh;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 4355998;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4355998-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 1/28/2016x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 4355998-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 1/28/2016x| ETDz| HERESOURCE;

Investigating intra- and inter-molecular coevolution of intrinsically disordered protein, Prothymosin-[alpha] / by Brianna Biscardi.

Author/creator	Biscardi, Brianna 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	80 pages : illustrations (some color)
Supplemental Content	Access via ScholarShip
Subjects	Proteins--Analysis. Coevolution. Myoglobin.

Summary	Prothymosin-[alpha] (ProT[alpha]) is a small, highly acidic protein found in the nuclei of virtually all mammalian tissues. It belongs to a class of proteins known for their lack of a rigid three-dimensional structure called intrinsically disordered proteins (IDPs). ProT[alpha] has been shown to play essential roles in cell robustness. As an example, ProT[alpha] is involved in apoptosis, or programmed cell death by inhibiting apoptosome formation via binding Apaf1. This research focus is on detecting coevolution of ProT[alpha] and between ProT[alpha] and Apaf1 (ProT[alpha]-Apaf1 or ProT[alpha]-Apaf1 complex). Coevolution refers to correlated changes between pairs of interacting species to maintain or refine functional interaction. Coevolution can be defined at the molecular level as correlated sequence changes that occur to maintain a structural or functional interaction. Studying coevolution of ProT[alpha] and ProT[alpha]-Apaf1 may provide useful information such as structural contacts and specific residues necessary for complex formation. In this study, a pipeline for performing molecular coevolution studies was established at East Carolina University (ECU). This pipeline was used to analyze myoglobin, ProT[alpha] and ProT[alpha]-Apaf1. Myoglobin has been a target of previous coevolutionary studies and was chosen to test the robustness of the pipeline developed in this study. Most of the coevolving residues that were found in myoglobin match closely with those detected in other work. ProT[alpha] which has never been studied by way of coevolution, displays several coevolving residues involved in long range interactions or functionally important regions. These methods were also applied to ProT[alpha] -Apaf1 complex. Previous experimental studies using 1H-15N heteronuclear single quantum coherence (HSQC) NMR have revealed residues on ProT[alpha] necessary for interaction with Apaf1 however the residues on Apaf1 necessary for interaction with ProT[alpha] have not been resolved. Several residues of ProT[alpha] were found to have coevolution with Apaf1. Docking studies were performed to simulate binding between ProT[alpha] and Apaf1 at the sites detected in this study (ProT[alpha],Thr8, Thr107; Apaf1: Ser1056, Asp1096). Six orientations of ProT[alpha] and Apaf1 were run for 9 nanoseconds (ns) and in each simulation, the two proteins did not drift apart from one another. This suggests that the residues detected by coevolution in this study may play a role in the interaction between ProT[alpha] and Apaf1.
General note	Presented to the faculty of the Department of Chemistry.
General note	Advisor: Colin S. Burns.
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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Investigating intra- and inter-molecular coevolution of intrinsically disordered protein, Prothymosin-[alpha] / by Brianna Biscardi.

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