4IC7

Crystal structure of the ERK5 kinase domain in complex with an MKK5 binding fragment

Summary for 4IC7

• Entry DOI: 10.2210/pdb4ic7/pdb
• Related: 4IC8
• Descriptor: Mitogen-activated protein kinase 7, Dual specificity mitogen-activated protein kinase kinase 5, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total)
• Functional Keywords: kinase domain, signaling protein complex, transferase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q13164
• Total number of polymer chains: 4
• Total formula weight: 128994.07

Authors

Gogl, G.,Remenyi, A. (deposition date: 2012-12-10, release date: 2013-02-13, Last modification date: 2024-02-28)

Primary citation

Glatz, G.,Gogl, G.,Alexa, A.,Remenyi, A.
Structural mechanism for the specific assembly and activation of the extracellular signal regulated kinase 5 (ERK5) module.
J.Biol.Chem., 288:8596-8609, 2013

PubMed 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.

PubMed: 23382384
DOI: 10.1074/jbc.M113.452235

Experimental method

X-RAY DIFFRACTION (2.6 Å)