Profilin binds proline-rich ligands in two distinct amide backbone orientations

The actin regulatory protein profilin is targeted to specific cellular regions through interactions with highly proline-rich motifs embedded within its binding partners. New X-ray crystallographic results demonstrate that profilin, like SH3 domains, can bind proline-rich ligands in two distinct amide backbone orientations. By further analogy with SH3 domains, these data suggest that non-proline residues in profilin ligands may dictate the polarity and register of binding, and the detailed organization of the assemblies involving profilin. This degeneracy may be a general feature of modules that bind proline-rich ligands, including WW and EVH1 domains, and has implications for the assembly and activity of macromolecular complexes involved in signaling and the regulation of the actin cytoskeleton.

[1]  L. Cooley,et al.  chickadee encodes a profilin required for intercellular cytoplasm transport during Drosophila oogenesis , 1992, Cell.

[2]  M. Carlier,et al.  Modulation of the interaction between G-actin and thymosin beta 4 by the ATP/ADP ratio: possible implication in the regulation of actin dynamics. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[3]  K. Gould,et al.  The Schizosaccharomyces pombe cdc3+ gene encodes a profilin essential for cytokinesis , 1994, The Journal of cell biology.

[4]  M. Sudol,et al.  Structure and function of the WW domain. , 1996, Progress in biophysics and molecular biology.

[5]  D. Weilguny,et al.  Characterization of fus1 of Schizosaccharomyces pombe: a developmentally controlled function needed for conjugation , 1995, Molecular and cellular biology.

[6]  Wendell A. Lim,et al.  Structural determinants of peptide-binding orientation and of sequence specificity in SH3 domains , 1995, Nature.

[7]  S. Schreiber,et al.  Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions. , 1995, Science.

[8]  K. Nakao,et al.  p140mDia, a mammalian homolog of Drosophila diaphanous,is a target protein for Rho small GTPase and is a ligand for profilin , 1997, The EMBO journal.

[9]  S V Evans,et al.  SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. , 1993, Journal of molecular graphics.

[10]  Wolfgang Kabsch,et al.  Evaluation of Single-Crystal X-ray Diffraction Data from a Position-Sensitive Detector , 1988 .

[11]  John R. Pringle,et al.  Bni1p, a Yeast Formin Linking Cdc42p and the Actin Cytoskeleton During Polarized Morphogenesis , 1997, Science.

[12]  D Cowburn,et al.  Modular peptide recognition domains in eukaryotic signaling. , 1997, Annual review of biophysics and biomolecular structure.

[13]  J. Calley,et al.  Profilin is required for posterior patterning of the Drosophila oocyte. , 1996, Development.

[14]  Steven C. Almo,et al.  Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation , 1997, Nature Structural Biology.

[15]  M. Sudol,et al.  The WW Domain of Neural Protein FE65 Interacts with Proline-rich Motifs in Mena, the Mammalian Homolog of DrosophilaEnabled* , 1997, The Journal of Biological Chemistry.

[16]  Marie-France Carlier,et al.  How profilin promotes actin filament assembly in the presence of thymosin β4 , 1993, Cell.

[17]  M. Saraste,et al.  Structure of the WW domain of a kinase-associated protein complexed with a proline-rich peptide , 1996, Nature.

[18]  U. Walter,et al.  The proline‐rich focal adhesion and microfilament protein VASP is a ligand for profilins. , 1995, The EMBO journal.

[19]  Fred Chang,et al.  cdc12p, a Protein Required for Cytokinesis in Fission Yeast, Is a Component of the Cell Division Ring and Interacts with Profilin , 1997, The Journal of cell biology.

[20]  T. Mitchison,et al.  The three faces of profilin , 1993, Cell.

[21]  J. Wehland,et al.  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 , 1997, The EMBO journal.

[22]  Hongtao Yu,et al.  Structural basis for the binding of proline-rich peptides to SH3 domains , 1994, Cell.

[23]  S. Wasserman,et al.  Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. , 1994, Development.

[24]  P. Leder,et al.  Formin binding proteins bear WWP/WW domains that bind proline‐rich peptides and functionally resemble SH3 domains. , 1996, The EMBO journal.

[25]  U. Walter,et al.  A focal adhesion factor directly linking intracellularly motile Listeria monocytogenes and Listeria ivanovii to the actin‐based cytoskeleton of mammalian cells. , 1995, The EMBO journal.

[26]  M. Sudol The WW module competes with the SH3 domain? , 1996, Trends in biochemical sciences.

[27]  J. Wehland,et al.  Mena, a Relative of VASP and Drosophila Enabled, Is Implicated in the Control of Microfilament Dynamics , 1996, Cell.

[28]  T. Adams,et al.  Identification of developmental regulatory genes in Aspergillus nidulans by overexpression. , 1995, Genetics.

[29]  T. Pollard,et al.  The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells. , 1992, Molecular biology of the cell.

[30]  B. Haarer,et al.  Purification of profilin from Saccharomyces cerevisiae and analysis of profilin-deficient cells , 1990, The Journal of cell biology.