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.
The ActA protein of the intracellular pathogen Listeria monocytogenes induces a dramatic reorganization of the actin-based cytoskeleton. Two profilin binding proteins, VASP and Mena, are the only cellular proteins known so far to bind directly to ActA. This interaction is mediated by a conserved module, the EVH1 domain. We identify E/DFPPPPXD/E, a motif repeated 4-fold within the primary sequence of ActA, as the core of the consensus ligand for EVH1 domains. This motif is also present and functional in at least two cellular proteins, zyxin and vinculin, which are in this respect major eukaryotic analogs of ActA. The functional importance of the novel protein-protein interaction was examined in the Listeria system. Removal of EVH1 binding sites on ActA reduces bacterial motility and strongly attenuates Listeria virulence. Taken together we demonstrate that ActA-EVH1 binding is a paradigm for a novel class of eukaryotic protein-protein interactions involving a proline-rich ligand that is clearly different from those described for SH3 and WW/WWP domains. This class of interactions appears to be of general importance for processes dependent on rapid actin remodeling.
Niebuhr
K
K
Abteilung Zellbiologie und Immunologie/AG Molekulare Erkennung, Mascheroder Weg 1, 38124 Braunschweig, Germany.
Ebel
F
F
Frank
R
R
Reinhard
M
M
Domann
E
E
Carl
U D
UD
Walter
U
U
Gertler
F B
FB
Wehland
J
J
Chakraborty
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006023:Glycoproteins; D006367:HeLa Cells; D006801:Humans; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008565:Membrane Proteins / Q000378:metabolism*; D008667:Metalloproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008840:Microfilament Proteins; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011392:Proline; D011485:Protein Binding; D017384:Sequence Deletion; D016596:Vinculin / Q000378:metabolism; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
D001426:Bacterial Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D006023:Glycoproteins; D008565:Membrane Proteins; D008667:Metalloproteins; D008840:Microfilament Proteins; D009842:Oligopeptides; D010750:Phosphoproteins; C092842:ZYX protein, human; C498285:Zyx protein, mouse; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D016596:Vinculin; C072980:actA protein, Listeria monocytogenes; D011392:Proline