General Information

Database Accession: DI1100045

Name: Homer EVH1 domain with bound Mglur peptide

PDB ID: 1ddv PDB

Experimental method: X-ray (1.90 Å)

Source organism: Rattus norvegicus

Proof of disorder: Inferred from motif

Primary publication of the structure:

Beneken J, Tu JC, Xiao B, Nuriya M, Yuan JP, Worley PF, Leahy DJ
Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition.

(2000) Neuron 26: 143-54

PMID: 10798399 PubMed


Homer EVH1 (Ena/VASP Homology 1) domains interact with proline-rich motifs in the cytoplasmic regions of group 1 metabotropic glutamate receptors (mGluRs), inositol-1,4,5-trisphosphate receptors (IP3Rs), and Shank proteins. We have determined the crystal structure of the Homer EVH1 domain complexed with a peptide from mGluR (TPPSPF). In contrast to other EVH1 domains, the bound mGluR ligand assumes an unusual conformation in which the side chains of the Ser-Pro tandem are oriented away from the Homer surface, and the Phe forms a unique contact. This unusual binding mode rationalizes conserved features of both Homer and Homer ligands that are not shared by other EVH1 domains. Site-directed mutagenesis confirms the importance of specific Homer residues for ligand binding. These results establish a molecular basis for understanding the biological properties of Homer-ligand complexes.

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

Molecular function:

G-protein coupled receptor binding Interacting selectively and non-covalently with a G-protein coupled receptor. GeneOntology

Biological process:

G-protein coupled glutamate receptor signaling pathway A series of molecular signals initiated by glutamate binding to a glutamate receptor on the surface of the target cell, and proceeding with the activated receptor promoting the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. Ends with regulation of a downstream cellular process, e.g. transcription. GeneOntology

Cellular component:

postsynaptic density of dendrite The postsynaptic density is a region that lies adjacent to the cytoplasmic face of the postsynaptic membrane at an excitatory synapse. It forms an electron-dense disc that consists of a range of proteins with different functions, some of which contact the cytoplasmic domains of ion channels in the postsynaptic membrane. The proteins making up the disc include structural proteins linked to the actin cytoskeleton and signalling machinery, such as protein kinases and phosphatases. GeneOntology

dendritic shaft Cylindric portion of the dendrite, directly stemming from the perikaryon, and carrying the dendritic spines. GeneOntology

postsynaptic membrane A specialized area of membrane facing the presynaptic membrane on the tip of the nerve ending and separated from it by a minute cleft (the synaptic cleft). Neurotransmitters cross the synaptic cleft and transmit the signal to the postsynaptic membrane. GeneOntology

intracellular The living contents of a cell; the matter contained within (but not including) the plasma membrane, usually taken to exclude large vacuoles and masses of secretory or ingested material. In eukaryotes it includes the nucleus and cytoplasm. 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: Metabotropic glutamate receptor 5 Disordered Inferred from motif

Source organism: Rattus norvegicus

Length: 6 residues

Sequence:Sequence according to PDB SEQRESTPPSPF

UniProtKB AC: P31424 (positions: 1155-1160) UniProt Coverage: 0.5%

UniRef90 AC: UniRef90_P31424 (positions: 1155-1160) UniRef90

Chain A

Name: Homer protein homolog 1 Ordered

Source organism: Rattus norvegicus

Length: 111 residues


UniProtKB AC: Q9Z214 (positions: 1-111) UniProt Coverage: 30.3%

UniRef90 AC: UniRef90_Q9Z214 (positions: 1-111) 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 (LIG_EVH1_2).

Chain A: Ordered

The WH1 domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00568). A solved monomeric structure of the domain is represented by PDB ID 1ddw.

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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