title: Heparin binding domain in vitronectin is required for oligomerization and thus enhances integrin mediated cell adhesion and spreading.
abstract: Vitronectin is a multi-functional protein found predominantly as a monomer in blood and as an oligomer in the extracellular matrix. We have dissected the minimal regions of vitronectin protein needed for effective integrin dependent cell adhesion and spreading. A fragment of vitronectin containing the RGD integrin binding site showed similar binding affinity as that of full vitronectin protein to purified integrin alphavbeta3 but had diminished cell adhesion and spreading function in vivo. We demonstrate that the oligomeric state of the protein is responsible for this effect. We provide compelling evidence for the involvement of the heparin binding domain of vitronectin in the oligomerization process and show that such oligomerization reinforces the activity of vitronectin in cell adhesion and spreading.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, The John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom.
authors.forename: Chandramouli R
authors.initials: CR
authors.lastname: Chillakuri
authors.forename: Céline
authors.initials: C
authors.lastname: Jones
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mardon
mesh_terms: D002448:Cell Adhesion; D002465:Cell Movement; D048430:Cell Shape; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D019096:Vitronectin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019096:Vitronectin; D006493:Heparin