Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2004-12-6
pubmed:abstractText
The glycoprotein Ib-IX-V (GP Ib-IX-V) complex mediates platelet binding to von Willebrand factor (VWF) through its largest polypeptide, GP Ibalpha. Of the many GP Ibalpha monoclonal antibodies described, AP1 is of particular interest because it blocks static VWF binding induced by 2 modulators, ristocetin and botrocetin, and platelet adhesion to VWF surfaces under flow. We mapped the AP1 binding site to a region encompassing Arg218 to Tyr228, comprising the alpha1 helix and beta13 strand defined by the GP Ibalpha crystal structure. AP1 binding absolutely required Arg218, Asp222, and Glu225. We evaluated the ability of cells expressing mutants of this region to bind VWF under static conditions in the presence of modulators, and to attach to and roll on a VWF matrix under flow. These data indicate that 2 regions within the sequence Arg218 to Tyr228 have important roles in VWF binding: the alpha1 helix has a regulatory role and the beta turn and beta13 strand bind VWF directly. Despite this, the only effect of a synthetic peptide corresponding to Leu214 to Val229 was to slightly increase the rolling velocity of GP Ibalpha-expressing Chinese hamster ovary (CHO) cells on VWF. This region thus appears to be more important for maintaining the regional conformation of GP Ibalpha, thereby facilitating the interaction with VWF.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Crotalid Venoms, http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ristocetin, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1, http://linkedlifedata.com/resource/pubmed/chemical/Valine, http://linkedlifedata.com/resource/pubmed/chemical/adhesion receptor, http://linkedlifedata.com/resource/pubmed/chemical/botrocetin, http://linkedlifedata.com/resource/pubmed/chemical/von Willebrand Factor
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3971-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15319289-Amino Acid Sequence, pubmed-meshheading:15319289-Amino Acid Substitution, pubmed-meshheading:15319289-Animals, pubmed-meshheading:15319289-Antibodies, Monoclonal, pubmed-meshheading:15319289-Binding Sites, pubmed-meshheading:15319289-CHO Cells, pubmed-meshheading:15319289-Cricetinae, pubmed-meshheading:15319289-Crotalid Venoms, pubmed-meshheading:15319289-Epitopes, pubmed-meshheading:15319289-Humans, pubmed-meshheading:15319289-Leucine, pubmed-meshheading:15319289-Membrane Glycoproteins, pubmed-meshheading:15319289-Membrane Proteins, pubmed-meshheading:15319289-Molecular Sequence Data, pubmed-meshheading:15319289-Mutagenesis, Site-Directed, pubmed-meshheading:15319289-Protein Binding, pubmed-meshheading:15319289-Protein Structure, Secondary, pubmed-meshheading:15319289-Recombinant Proteins, pubmed-meshheading:15319289-Ristocetin, pubmed-meshheading:15319289-Transcription Factor AP-1, pubmed-meshheading:15319289-Valine, pubmed-meshheading:15319289-von Willebrand Factor
pubmed:year
2004
pubmed:articleTitle
The alpha1 helix-beta13 strand spanning Leu214 to Val229 of platelet glycoprotein Ibalpha facilitates the interaction with von Willebrand factor: evidence from characterization of the epitope of monoclonal antibody AP1.
pubmed:affiliation
Thrombosis Research Section, Baylor College of Medicine, BCM 286, N1319, 1 Baylor Plaza, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.