title: The heparin-binding domain confers diverse functions of VEGF-A in development and disease: a structure-function study.
abstract: The longer splice isoforms of VEGF (vascular endothelial growth factor)-A, including VEGF(164(165)), contain a highly basic HBD (heparin-binding domain). This domain allows these isoforms to interact with and localize to the HS (heparan sulfate)-rich extracellular matrix, and bind to the co-receptor Nrp-1 (neuropilin-1). Heparin-binding VEGF-A isoforms are critical for survival: mice engineered to express exclusively the non-heparin-binding VEGF(120) have diminished vascular branching during embryonic development and die from postnatal angiogenesis defects shortly after birth. Although it is thought that the HBD contributes to the diverse functions of VEGF-A in both physiological and pathological processes, little is known about the molecular features within this domain that enable these functions. In the present paper, we discuss the roles of the VEGF HBD in normal and disease conditions, with a particular focus on the VEGF(164(165)) isoform.
authors.affiliation: Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Dominik
authors.initials: D
authors.lastname: Krilleke
authors.forename: Yin-Shan Eric
authors.initials: YS
authors.lastname: Ng
authors.forename: David T
authors.initials: DT
authors.lastname: Shima
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D005128:Eye Diseases / Q000378:metabolism / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D019812:Heparan Sulfate Proteoglycans; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin