PDBsum entry 2xs0

Transcription

PDB id: 2xs0

Contents

Protein chains

346 a.a.

12 a.a.

Ligands

ANP

Waters ×18

PDB id:

2xs0

Name:

Transcription

Title:

Linear binding motifs for jnk and for calcineurin antagonistically control the nuclear shuttling of nfat4

Structure:

Mitogen-activated protein kinase 8. Chain: a. Synonym: map kinase 8, mapk 8, stress-activated protein kinase jnk1, jnk1, c-jun n-terminal kinase 1, jnk-46, stress-activated protein kinase 1. Engineered: yes. Mutation: yes. Nuclear factor of activated t-cells, cytoplasmic 3. Chain: b.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta plyss. Synthetic: yes. Organism_taxid: 9606

Resolution:

2.60Å R-factor: 0.194 R-free: 0.246

Authors:

T.Barkai,I.Toeoroe,A.Garai,A.Remenyi

Key ref:

�.�.Garai et al. (2012). Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove. Sci Signal, 5, ra74. PubMed id: 23047924

Date:

24-Sep-10 Release date: 28-Sep-11

Protein chain

P45983  (MK08_HUMAN) -  Mitogen-activated protein kinase 8 from Homo sapiens

Seq: 427 a.a.

Struc: 346 a.a.*

Protein chain

Q12968  (NFAC3_HUMAN) -  Nuclear factor of activated T-cells, cytoplasmic 3 from Homo sapiens

Seq: 1075 a.a.

Struc: 12 a.a.

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chain A: E.C.2.7.11.24 - mitogen-activated protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = ANP) matches with 81.25% similarity) + ADP + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Sci Signal 5:ra74 (2012)

PubMed id: 23047924

Specificity of linear motifs that bind to a common mitogen-activated protein kinase docking groove.

�.�.Garai, A.Zeke, G.Gógl, I.Törő, F.Fördős, H.Blankenburg, T.Bárkai, J.Varga, A.Alexa, D.Emig, M.Albrecht, A.Reményi.

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.