NDLI: Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) $Module^{*}$

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Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) $Module^{*}$

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Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) $Module^{*}$

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Alexa, Anita Reményi, Attila Glatz, Gábor Gógl, Gergo
Description	Author Affiliation: Glatz G ( Department of Biochemistry, Eötvös Loránd University, Budapest H-1117, Hungary.)
Abstract	Mitogen-activated protein kinase (MAPK) activation depends on a linear binding motif found in all MAPK kinases (MKK). In addition, the PB1 (Phox and Bem1) domain of MKK5 is required for extracellular signal regulated kinase 5 (ERK5) activation. We present the crystal structure of ERK5 in complex with an MKK5 construct comprised of the PB1 domain and the linear binding motif. We show that ERK5 has distinct protein-protein interaction surfaces compared with ERK2, which is the closest ERK5 paralog. The two MAPKs have characteristically different physiological functions and their distinct protein-protein interaction surface topography enables them to bind different sets of activators and substrates. Structural and biochemical characterization revealed that the MKK5 PB1 domain cooperates with the MAPK binding linear motif to achieve substrate specific binding, and it also enables co-recruitment of the upstream activating enzyme and the downstream substrate into one signaling competent complex. Studies on present day MAPKs and MKKs hint on the way protein kinase networks may evolve. In particular, they suggest how paralogous enzymes with similar catalytic properties could acquire novel signaling roles by merely changing the way they make physical links to other proteins.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	12
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-03-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Mitogen-Activated Protein Kinase 7 Chemistry Models, Molecular Amino Acid Sequence Apoenzymes Catalytic Domain Crystallography, X-Ray Enzyme Activation HEK293 Cells MAP Kinase Kinase 5 MAP Kinase Signaling System Mitogen-Activated Protein Kinase 1 Molecular Sequence Data Multiprotein Complexes Protein Binding Protein Interaction Domains And Motifs Protein Multimerization Protein Structure, Quaternary Protein Structure, Secondary Surface Properties Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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