2.50
Hdl Handle:
http://hdl.handle.net/10033/344410
Title:
Structure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase.
Authors:
Patel, Ashok K; Yadav, Ravi P; Majava, Viivi; Kursula, Inari ( 0000-0001-5236-7056 ) ; Kursula, Petri ( 0000-0001-8529-3751 )
Abstract:
The death-associated protein kinase (DAPK) family has been characterized as a group of pro-apoptotic serine/threonine kinases that share specific structural features in their catalytic kinase domain. Two of the DAPK family members, DAPK1 and DAPK2, are calmodulin-dependent protein kinases that are regulated by oligomerization, calmodulin binding, and autophosphorylation. In this study, we have determined the crystal and solution structures of murine DAPK2 in the presence of the autoinhibitory domain, with and without bound nucleotides in the active site. The crystal structure shows dimers of DAPK2 in a conformation that is not permissible for protein substrate binding. Two different conformations were seen in the active site upon the introduction of nucleotide ligands. The monomeric and dimeric forms of DAPK2 were further analyzed for solution structure, and the results indicate that the dimers of DAPK2 are indeed formed through the association of two apposed catalytic domains, as seen in the crystal structure. The structures can be further used to build a model for DAPK2 autophosphorylation and to compare with closely related kinases, of which especially DAPK1 is an actively studied drug target. Our structures also provide a model for both homodimerization and heterodimerization of the catalytic domain between members of the DAPK family. The fingerprint of the DAPK family, the basic loop, plays a central role in the dimerization of the kinase domain.
Citation:
Structure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase. 2011, 409 (3):369-83 J. Mol. Biol.
Journal:
Journal of molecular biology
Issue Date:
10-Jun-2011
URI:
http://hdl.handle.net/10033/344410
DOI:
10.1016/j.jmb.2011.03.065
PubMed ID:
21497605
Type:
Article
Language:
en
ISSN:
1089-8638
Appears in Collections:
publications of the research group CSSB

Full metadata record

DC FieldValue Language
dc.contributor.authorPatel, Ashok Ken
dc.contributor.authorYadav, Ravi Pen
dc.contributor.authorMajava, Viivien
dc.contributor.authorKursula, Inarien
dc.contributor.authorKursula, Petrien
dc.date.accessioned2015-02-12T12:38:59Zen
dc.date.available2015-02-12T12:38:59Zen
dc.date.issued2011-06-10en
dc.identifier.citationStructure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase. 2011, 409 (3):369-83 J. Mol. Biol.en
dc.identifier.issn1089-8638en
dc.identifier.pmid21497605en
dc.identifier.doi10.1016/j.jmb.2011.03.065en
dc.identifier.urihttp://hdl.handle.net/10033/344410en
dc.description.abstractThe death-associated protein kinase (DAPK) family has been characterized as a group of pro-apoptotic serine/threonine kinases that share specific structural features in their catalytic kinase domain. Two of the DAPK family members, DAPK1 and DAPK2, are calmodulin-dependent protein kinases that are regulated by oligomerization, calmodulin binding, and autophosphorylation. In this study, we have determined the crystal and solution structures of murine DAPK2 in the presence of the autoinhibitory domain, with and without bound nucleotides in the active site. The crystal structure shows dimers of DAPK2 in a conformation that is not permissible for protein substrate binding. Two different conformations were seen in the active site upon the introduction of nucleotide ligands. The monomeric and dimeric forms of DAPK2 were further analyzed for solution structure, and the results indicate that the dimers of DAPK2 are indeed formed through the association of two apposed catalytic domains, as seen in the crystal structure. The structures can be further used to build a model for DAPK2 autophosphorylation and to compare with closely related kinases, of which especially DAPK1 is an actively studied drug target. Our structures also provide a model for both homodimerization and heterodimerization of the catalytic domain between members of the DAPK family. The fingerprint of the DAPK family, the basic loop, plays a central role in the dimerization of the kinase domain.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshApoptosisen
dc.subject.meshApoptosis Regulatory Proteinsen
dc.subject.meshCalcium-Calmodulin-Dependent Protein Kinasesen
dc.subject.meshCatalytic Domainen
dc.subject.meshCrystallography, X-Rayen
dc.subject.meshDeath-Associated Protein Kinasesen
dc.subject.meshDimerizationen
dc.subject.meshMiceen
dc.subject.meshModels, Molecularen
dc.subject.meshPhosphorylationen
dc.subject.meshProtein Conformationen
dc.subject.meshProtein Interaction Domains and Motifsen
dc.subject.meshSequence Homology, Amino Aciden
dc.titleStructure of the dimeric autoinhibited conformation of DAPK2, a pro-apoptotic protein kinase.en
dc.typeArticleen
dc.identifier.journalJournal of molecular biologyen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.