title: NOE-derived conformation of GRGDSP cell adhesion recognition site in the presence of SDS micelles and integrin receptor GPIIB/IIIA.
abstract: The tripeptide RGD is well known for its role in integrin receptor-mediated cell-cell surface adhesion. Here, NMR and transferred NOE studies have been done with the fibrinogen/fibronectin-derived hexapeptide GRGDSP in the presence of sodium dodecyl sulfate (SDS) and purified platelet glycoprotein integrin receptor GPIIb/IIIa. In the presence of SDS and absence of receptor, GRGDSP gives NOE-based distance geometry-generated structures characteristic of two "nested' beta-turns centered at RG and GD. In the presence of integrin GPIIb/IIIa, GRGDSP resonances are chemically shifted and broadened consistent with a dynamic equilibrium between free and receptor "bound' peptide. NOEs characteristic of the nested beta-turns are either absent or weaker indicating a significant conformational change in GRGDSP in the receptor bound state. GRGDSP appears to bind the receptor in a more extended backbone conformation which positions aspartic acid and arginine residues spatially close for potential electrostatic interactions.
authors.affiliation: Department of Biochemistry, Biomedical Engineering Center, University of Minnesota, MN 55455, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Mayo
authors.forename: F
authors.initials: F
authors.lastname: Fan
authors.forename: M P
authors.initials: MP
authors.lastname: Beavers
authors.forename: A
authors.initials: A
authors.lastname: Eckardt
authors.forename: P
authors.initials: P
authors.lastname: Keane
authors.forename: W J
authors.initials: WJ
authors.lastname: Hoekstra
authors.forename: P
authors.initials: P
authors.lastname: Andrade-Gordon
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D012984:Software
chemical_list: D009842:Oligopeptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline