title: The C-terminal polyproline-containing region of ELMO contributes to an increase in the life-time of the ELMO-DOCK complex.
abstract: The eukaryotic Engulfment and CellMotility (ELMO) proteins form an evolutionary conserved family of key regulators which play a central role in Rho-dependent biological processes such as engulfment and cell motility/migration. ELMO proteins interact with a subset of Downstream of Crk (DOCK) family members, a new type of guanine exchange factors (GEF) for Rac and cdc42 GTPases. The physiological function of DOCK is to facilitate actin remodeling, a process which occurs only in presence of ELMO. Several studies have determined that the last 200 C-terminal residues of ELMO1 and the first 180 N-terminal residues of DOCK180 are responsible for the ELMO-DOCK interaction. However, the precise role of the different domains and motifs identified in these regions has remained elusive. Divergent functional, biochemical and structural data have been reported regarding the contribution of the C-terminal end of ELMO, comprising its polyproline motif, and of the DOCK SH3 domain. In the present study, we have investigated the contribution of the C-terminal end of ELMO1 to the interaction between ELMO1 and the SH3 domain of DOCK180 using nuclear magnetic resonance spectroscopy and surface plasmon resonance. Our data presented here demonstrate the ability of the SH3 domain of DOCK180 to interact with ELMO1, regardless of the presence of the polyproline-containing C-terminal end. However, the presence of the polyproline region leads to a significant increase in the half-life of the ELMO1-DOCK180 complex, along with a moderate increase on the affinity.
authors.affiliation: Immune response to pathogens and altered-self group, Institut de Biologie Structurale Jean-Pierre Ebel, Commissariat à l'Energie Atomique et aux Energies Alternatives, Centre National de la Recherche Scientifique, Université Joseph Fourier-Grenoble 1, 41, rue Jules Horowitz, F-38027 Grenoble, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Sévajol
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Reiser
authors.forename: Anne
authors.initials: A
authors.lastname: Chouquet
authors.forename: Julien
authors.initials: J
authors.lastname: Pérard
authors.forename: Isabel
authors.initials: I
authors.lastname: Ayala
authors.forename: Pierre
authors.initials: P
authors.lastname: Gans
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Kleman
authors.forename: Dominique
authors.initials: D
authors.lastname: Housset
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C528110:Dock180 protein, mouse; C510359:ELMO1 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D010455:Peptides; C011083:polyproline