2Y8O

Crystal structure of human p38alpha complexed with a MAPK docking peptide

Summary for 2Y8O

• Entry DOI: 10.2210/pdb2y8o/pdb
• Related: 1A9U 1BL6 1BL7 1BMK 1DI9 1IAN 1KV1 1KV2 1M7Q 1OUK 1OUY 1OVE 1OZ1 1R39 1R3C 1W7H 1W82 1W83 1W84 1WBN 1WBO 1WBS 1WBT 1WBV 1WBW 1WFC 1YQJ 1ZYJ 1ZZ2 1ZZL 2BAJ 2BAK 2BAL 2BAQ 2I0H 2YIS 2YIW 2YIX 3ZS5 3ZSG 3ZSH 3ZSI 3ZYA 4AA0 4AA4 4AA5 4AAC
• Descriptor: MITOGEN-ACTIVATED PROTEIN KINASE 14, DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 6 (3 entities in total)
• Functional Keywords: transferase, signalling, map kinase pathway, protein-protein interaction
• Biological source: Homo sapiens (HUMAN); More
• Cellular location: Cytoplasm : Q16539; Nucleus : P52564
• Total number of polymer chains: 2
• Total formula weight: 43028.20

Authors

Barkai, T.,Garai, A.,Toeroe, I.,Remenyi, A. (deposition date: 2011-02-08, release date: 2012-02-22, Last modification date: 2023-12-20)

Primary citation

Garai, A.,Zeke, A.,Gogl, G.,Toro, I.,Fordos, F.,Blankenburg, H.,Barkai, T.,Varga, J.,Alexa, A.,Emig, D.,Albrecht, M.,Remenyi, A.
Specificity of Linear Motifs that Bind to a Common Mitogen-Activated Protein Kinase Docking Groove.
Sci. Signal, 5:74-, 2012

PubMed Abstract: Mitogen-activated protein kinases (MAPKs) have a docking groove that interacts with linear "docking" motifs in binding partners. To determine the structural basis of binding specificity between MAPKs and docking motifs, we quantitatively analyzed the ability of 15 docking motifs from diverse MAPK partners to bind to c-Jun amino-terminal kinase 1 (JNK1), p38α, and extracellular signal-regulated kinase 2 (ERK2). Classical docking motifs mediated highly specific binding only to JNK1, and only those motifs with a sequence pattern distinct from the classical MAPK binding docking motif consensus differentiated between the topographically similar docking grooves of ERK and p38α. Crystal structures of four complexes of MAPKs with docking peptides, representing JNK-specific, ERK-specific, or ERK- and p38-selective binding modes, revealed that the regions located between consensus positions in the docking motifs showed conformational diversity. Although the consensus positions in the docking motifs served as anchor points that bound to common MAPK surface features and mostly contributed to docking in a nondiscriminatory fashion, the conformation of the intervening region between the anchor points mostly determined specificity. We designed peptides with tailored MAPK binding profiles by rationally changing the length and amino acid composition of intervening regions located between anchor points. These results suggest a coherent structural model for MAPK docking specificity that reveals how short linear motifs binding to a common kinase docking groove can mediate diverse interaction patterns and contribute to correct MAPK partner selection in signaling networks.

PubMed: 23047924
DOI: 10.1126/SCISIGNAL.2003004

Experimental method

X-RAY DIFFRACTION (1.95 Å)