title: Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation.
abstract: Profilin, a ubiquitous low molecular weight (13,000-15,000 M(r)) actin binding protein, regulates the formation of F-actin structures in vivo, and is localized to specific cellular regions through interaction with proline-rich sequences. Here we report the 2.2 A X-ray structure of the complex between human platelet profilin (HPP) and a decamer of L-proline (L-Pro10). The L-Pro10 peptide adopts a left-handed type II poly-L-proline helix (PPII) and binds to a highly conserved patch of aromatic amino acids on the surface of profilin. The peptide and actin binding sites reside on orthogonal surfaces, and L-Pro10 binding does not result in a conformational rearrangement of HPP. This structure suggests a mechanism for the localization of profilin and its actin-related activities to sites of actin filament assembly in vivo.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Mahoney
authors.forename: P A
authors.initials: PA
authors.lastname: Janmey
authors.forename: S C
authors.initials: SC
authors.lastname: Almo
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets / Q000737:chemistry; D003285:Contractile Proteins; D018360:Crystallography, X-Ray; D003599:Cytoskeleton; D006801:Humans; D008024:Ligands; D008027:Light; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D051304:Profilins; D011392:Proline / Q000737:chemistry; D017433:Protein Structure, Secondary; D012542:Scattering, Radiation; D016415:Sequence Alignment
chemical_list: D003285:Contractile Proteins; D008024:Ligands; D008840:Microfilament Proteins; D009842:Oligopeptides; C495738:PFN1 protein, human; D010455:Peptides; D051304:Profilins; C011083:polyproline; D011392:Proline