3TG1

Crystal structure of p38alpha in complex with a MAPK docking partner

Summary for 3TG1

• Entry DOI: 10.2210/pdb3tg1/pdb
• Related: 3TG3
• Descriptor: Mitogen-activated protein kinase 14, Dual specificity protein phosphatase 10 (3 entities in total)
• Functional Keywords: kinase/rhodanese-like domain, docking interaction, transferase-hydrolase complex, transferase/hydrolase
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm: P47811 Q9Y6W6
• Total number of polymer chains: 2
• Total formula weight: 61584.44

Authors

Zhang, Y.Y.,Wu, J.W.,Wang, Z.X. (deposition date: 2011-08-17, release date: 2012-03-14, Last modification date: 2023-11-01)

Primary citation

Zhang, Y.Y.,Wu, J.W.,Wang, Z.X.
A Distinct Interaction Mode Revealed by the Crystal Structure of the Kinase p38alpha with the MAPK Binding Domain of the Phosphatase MKP5.
Sci.Signal., 4:ra88-ra88, 2011

PubMed Abstract: The mitogen-activated protein kinase (MAPK) cascades play a pivotal role in a myriad of cellular functions. The specificity and efficiency of MAPK signaling are controlled by docking interactions between MAPKs and their cognate proteins. Many MAPK-interacting partners, including substrates, MAPK kinases, phosphatases, and scaffolding proteins, have linear sequence motifs that mediate the interaction with the common docking site on MAPKs. We report the crystal structure of p38α in complex with the MAPK binding domain (KBD) from MAPK phosphatase 5 (MKP5) at 2.7 Å resolution. In contrast to the well-known docking mode, the KBD binds p38α in a bipartite manner, in which two distinct helical regions of KBD engage the p38α docking site, which is situated on the back of the p38α active site. We also determined the crystal structure of the KBD of MKP7, which closely resembles the MKP5 KBD, suggesting that the mechanism of molecular recognition by the KBD of MKP5 is conserved in the cytoplasmic p38- and c-Jun N-terminal kinase-specific MKP subgroup. This previously unknown binding mode provides new insights into how MAPKs interact with their binding partners to achieve functional specificity.

PubMed: 22375048
DOI: 10.1126/scisignal.2002241

Experimental method

X-RAY DIFFRACTION (2.71 Å)