EVH1 Domain

First identified in the Ena/VASP family of proteins in Drosophila, the EVH1 domain is a c110 amino acid sequence that binds poly-proline rich regions recognised by a variety of binding partners. Confusingly, VASP itself contains proline-rich sequences that bind profilin (a small actin monomer binding protein), certain SH3 and WW domains. The EVH1 domain recognises (F/L/W/Y)PPPP and does not recognise the proline-rich regions in VASP itself.

Protein	Function	Binding partner	Reference

Enabled/VASP	Focal adhesion proteins	Zyxin, Vinculin	Niebuhr et al, 1997
	A Listeria protein used to subvert the cytoskeleton in order to propel the bacterium into other cells.	ActA	Niebuhr et al, 1997
Mena
Homer	Enriched in the post synaptic density of dendritic spines where it complexes with SHANK proteins (see Dendritic spines)
Sprouty
Spred
WASP	Pivotally involved in actin polymerization together with the Arp2/3 complex.
Table 1 EVH1 containing proteins and their partners

The structure of the EVH1 domain has been solved with the poly-proline target (Preholda et al, 1999; Beneken et al, 2000), surprisingly it has been noticed (Preholda et al, 1999) that this structure is similar to the structure of the PH domain despite very low sequence homology, and quite distinct in stucture to the SH3 domain. This is despite the fact that both the EVH1 and the SH3 domains bind proline rich sequences through interaction of aromatic residues.

References:-

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, 143-154.

Niebuhr, K., Ebel, F., Frank, R., Reinhard, M., Domann, E., Carl, U. D., Walter, U., Gertler, F. B., Wehland, J. & Chakraborty, T. (1997) A novel proline-rich motif present in ActA of Listeria monocytogenes and cytoskeletal proteins is the ligand for the EVH1 domain, a protein module present in the Ena/VASP family, EMBO J. 16, 5433-5444.

Prehoda, K. E., Lee, D. J. & Lim, W. A. (1999) Structure of the enabled/VASP homolgy 1 domain-peptide complex: A key component in the spatial control of actin assembly., Cell. 97, 471-480.

Renfranz, P. J. & Beckerle, M. C. (2002) Doing (F/L)PPPPs: EVH1 domains and their proline-rich partners in cell polarity and migration., Curr.Op.Cell Biol. 14, 88-103.