title: A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding.
abstract: P-selectin glycoprotein ligand 1 (PSGL-1) is a mucin-like glycoprotein expressed on the surface of myeloid cells and serves as the high affinity counterreceptor for P-selectin. The PSGL-1-P-selectin interaction is calcium dependent and requires presentation of sialyl-Lewisx (sLex)-type structures on the O-linked glycans of PSGL-1. We report here the identification of a non-carbohydrate component of the binding determinant that is critical for high affinity binding to P-selectin. Located within the first 19 amino acids, this anionic polypeptide segment contains at least one sulfated tyrosine residue. We propose that this sulfotyrosine-containing segment of PSGL-1, in conjunction with sLex presented on O-linked glycans, constitutes the high affinity P-selectin-binding site.
authors.affiliation: Genetics Institute, Small Molecule Drug Discovery Group, Cambridge, Massachusetts 02140, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sako
authors.forename: K M
authors.initials: KM
authors.lastname: Comess
authors.forename: K M
authors.initials: KM
authors.lastname: Barone
authors.forename: R T
authors.initials: RT
authors.lastname: Camphausen
authors.forename: D A
authors.initials: DA
authors.lastname: Cumming
authors.forename: G D
authors.initials: GD
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004252:DNA Mutational Analysis; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D010455:Peptides; D011993:Recombinant Fusion Proteins; C005662:tyrosine O-sulfate; D014443:Tyrosine; D009439:Neuraminidase