General Information

Database Accession: DI1010079

Name: Docking motif interactions in the MAP kinase ERK2

PDB ID: 2gph PDB

Experimental method: X-ray (1.90 Å)

Source organism: Homo sapiens / Rattus norvegicus

Proof of disorder: Inferred from motif

K_d: 6.30×10^-06 M PubMed

Primary publication of the structure:

Zhou T, Sun L, Humphreys J, Goldsmith EJ
Docking interactions induce exposure of activation loop in the MAP kinase ERK2.
(2006) Structure 14: 1011-9

PMID: 16765894 PubMed

Abstract:

MAP kinases bind activating kinases, phosphatases, and substrates through docking interactions. Here, we report a 1.9 A crystallographic analysis of inactive ERK2 bound to a "D motif" docking peptide (pepHePTP) derived from hematopoietic tyrosine phosphatase, a negative regulator of ERK2. In this complex, the complete D motif interaction defined by mutagenic analysis is observed, including extensive electrostatic interactions with the "CD" site of the kinase. Large conformational changes occur in the activation loop where the dual phosphorylation sites, which are buried in the inactive form of ERK2, become exposed to solvent in the complex. Similar conformational changes occur in a complex between ERK2 and a MEK2 (MAP/ERK kinase-2)-derived D motif peptide (pepMEK2). D motif peptides are known to bind homologous loci in the MAP kinases p38alpha and JNK1, also inducing conformational changes in these enzymes. However, the binding interactions and conformational changes are unique to each, thus contributing to specificity among MAP kinases.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

protein binding Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). GeneOntology

Biological process:

cellular protein modification process The covalent alteration of one or more amino acids occurring in proteins, peptides and nascent polypeptides (co-translational, post-translational modifications) occurring at the level of an individual cell. Includes the modification of charged tRNAs that are destined to occur in a protein (pre-translation modification). GeneOntology

phosphate-containing compound metabolic process The chemical reactions and pathways involving the phosphate group, the anion or salt of any phosphoric acid. GeneOntology

Cellular component:

cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. GeneOntology

cytoskeleton Any of the various filamentous elements that form the internal framework of cells, and typically remain after treatment of the cells with mild detergent to remove membrane constituents and soluble components of the cytoplasm. The term embraces intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. GeneOntology

plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

Entry contents: 2 distinct polypeptide molecules

Chains: B, A

Notes: No modifications of the original PDB file.

Chain B

Name: Tyrosine-protein phosphatase non-receptor type 7 Disordered Inferred from motif

Source organism: Homo sapiens

Length: 16 residues

Sequence:Sequence according to PDB SEQRESRLQERRGSNVALMLDC

UniProtKB AC: P35236 (positions: 37-52) UniProt Coverage: 4.4%

UniRef90 AC: UniRef90_P35236 (positions: 37-52) UniRef90

Chain A

Name: Mitogen-activated protein kinase 1 Ordered

Source organism: Rattus norvegicus

Length: 357 residues

Sequence:Sequence according to PDB SEQRESAAAAAAGPEMVRGQVFDVGPRYTNLSYIGEGAYGMVCSAYDNLNKVRVAIKKISPFEHQTYCQRTLREIKILLRFRHENIIGINDIIRAPTIEQMKDVYIVQDLMETDLYKLLKTQHLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTTCDLKICDFGLARVADPDHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLSNRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINLKARNYLLSLPHKNKVPWNRLFPNADSKALDLLDKMLTFNPHKRIEVEQALAHPYLEQYYDPSDEPIAEAPFKFDMELDDLPKEKLKELIFEETARFQPGYRS

UniProtKB AC: P63086 (positions: 2-358) UniProt Coverage: 99.7%

UniRef90 AC: UniRef90_P28482 (positions: 2-358) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain B: Disordered Inferred from motif

The protein region involved in the interaction contains a known functional linear motif (DOC_MAPK_HePTP_8).

Chain A: Ordered

The Protein kinase domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00069). A solved monomeric structure of the domain is represented by PDB ID 1erk.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

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