Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition

Jutta Beneken, Jian Cheng Tu, Bo Xiao, Mutsuo Nuriya, Joseph P. Yuan, Paul F. Worley, Daniel J. Leahy

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)143-154
Number of pages12
JournalNeuron
Volume26
Issue number1
Publication statusPublished - 2000
Externally publishedYes

Fingerprint

Ligands
seryl-proline
Inositol 1,4,5-Trisphosphate Receptors
Site-Directed Mutagenesis
Proline
Peptides
polyproline
Protein Domains
Proteins
metabotropic glutamate receptor type 1

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Beneken, J., Tu, J. C., Xiao, B., Nuriya, M., Yuan, J. P., Worley, P. F., & Leahy, D. J. (2000). Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. Neuron, 26(1), 143-154.

Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. / Beneken, Jutta; Tu, Jian Cheng; Xiao, Bo; Nuriya, Mutsuo; Yuan, Joseph P.; Worley, Paul F.; Leahy, Daniel J.

In: Neuron, Vol. 26, No. 1, 2000, p. 143-154.

Research output: Contribution to journalArticle

Beneken, J, Tu, JC, Xiao, B, Nuriya, M, Yuan, JP, Worley, PF & Leahy, DJ 2000, 'Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition', Neuron, vol. 26, no. 1, pp. 143-154.
Beneken, Jutta ; Tu, Jian Cheng ; Xiao, Bo ; Nuriya, Mutsuo ; Yuan, Joseph P. ; Worley, Paul F. ; Leahy, Daniel J. / Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. In: Neuron. 2000 ; Vol. 26, No. 1. pp. 143-154.
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