Kinase-interacting FHA domain of kinase associated protein phosphatase: phosphopeptide interactions and NMR-detected dynamics

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Kinase-interacting FHA domain of kinase associated protein phosphatase: phosphopeptide interactions and NMR-detected dynamics

Please use this identifier to cite or link to this item: http://hdl.handle.net/10355/4729

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dc.contributor.advisor Van Doren, Steven en
dc.contributor.author Ding, Zhaofeng, 1978- en_US
dc.date.accessioned 2010-01-12T18:41:15Z
dc.date.available 2010-01-12T18:41:15Z
dc.date.issued 2007 en_US
dc.date.submitted 2007 Spring en
dc.identifier.other DingZ-020907-D7393 en_US
dc.identifier.uri http://hdl.handle.net/10355/4729
dc.description The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. en_US
dc.description Title from title screen of research.pdf file (viewed on September 24, 2007) en_US
dc.description Vita. en_US
dc.description Includes bibliographical references. en_US
dc.description Thesis (Ph. D.) University of Missouri-Columbia 2007. en_US
dc.description Dissertations, Academic -- University of Missouri--Columbia -- Biochemistry (Agriculture) en_US
dc.description.abstract FHA domains are phosphoThr recognition modules found in diverse signaling proteins. Kinase-associated protein phosphatase (KAPP) from Arabidopsis employs its FHA domain in its negative regulation of some receptor-like kinase (RLK) signaling pathways. The interactions between the kinase-interacting FHA (KI-FHA) domain of KAPP and RLK kinase domains have been investigated. Three phosphoThr peptides of KAPP-binding RLKs were found by isothermal titration calorimetry (ITC) and NMR to bind KI-FHA, with Kd values of 8 to 30 [mu]M. Thermodynamics study revealed that their affinities were driven by favorable enthalpy and the hydrophobic effect. Mutagenesis of these three threonine sites suggests Thr546 in the C-lobe of BAK1 kinase domain to be a principal site of KI-FHA binding. BRI1 kinase domain interacts with the same 3/4, 4/5, 6/7, 8/9, and 10/11 recognition loops of KI-FHA as do phosphoThr peptides. The backbone mobility of KI-FHA, free and bound to pThr868CLV1 peptide has also been investigated using 15N NMR relaxation at 500 MHz and 600 MHz. Binding of the peptide seems to reduce nsec-scale fluctuations of KI-FHA globally. In the psec to nsec timescale, KI-FHA residues that are critical for phosphopeptide recognitions are rigid. Peptide binding rigidifies KI-FHA at the binding site and remote sites across the [beta-] sandwich. Peptide binding increases flexibility around the periphery of the binding site, perhaps relieving strain from the peptide association. en_US
dc.language.iso en_US en_US
dc.publisher University of Missouri--Columbia en_US
dc.subject Forkhead-associated domain. en_US
dc.subject Forkhead-associated domain en_US
dc.subject.lcsh Plants -- Development en_US
dc.subject.lcsh Phosphoprotein phosphatases en_US
dc.subject.lcsh Protein kinases en_US
dc.subject.lcsh Nuclear magnetic resonance en_US
dc.subject.lcsh Cellular signal transduction en_US
dc.subject.lcsh Mutagenesis en_US
dc.title Kinase-interacting FHA domain of kinase associated protein phosphatase: phosphopeptide interactions and NMR-detected dynamics en_US
dc.type Thesis en_US
thesis.degree.discipline Biochemistry (Agriculture) en_US
thesis.degree.grantor University of Missouri--Columbia en_US
thesis.degree.name Ph. D. en_US
thesis.degree.level Doctoral en_US
dc.identifier.merlin .b59729776 en_US
dc.identifier.oclc 173259136 en_US
dc.relation.ispartofcommunity University of Missouri-Columbia. Graduate School. Theses and Dissertations. Dissertations. 2007 Dissertations
dc.relation.ispartofcollection 2007 Freely available dissertations (MU)


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