tailieunhanh - Báo cáo khoa hoc : Tying the knot The cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines

The cystine-knot motif, made up of three intertwined disulfide bridges, is a unique feature of several toxins, cyclotides and growth factors, and occurs in a variety of species, including fungi, insects, molluscs and mammals. Growth factor molecules containing the cystine-knot motif serve as ligands for a diverse range of receptors and play an important role in extracellular signalling. | IFEBS Journal REVIEW ARTICLE Tying the knot The cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines Shalini Iyer and K. Ravi Acharya Department of Biology and Biochemistry University of Bath Claverton Down Bath UK Keywords angiogenesis cystine-knot growth factors molecular recognition vascular endothelial growth factor VEGF family VEGF receptors Correspondence K. R. Acharya Department of Biology and Biochemistry University of Bath Claverton Down Bath BA2 7AY UK Fax 44 1225 386779 Tel 44 1225 386238 E-mail bsskra@ Re-use of this article is permitted in accordance with the Terms and Conditions set out at http onlineopen OnlineOpen_Terms The cystine-knot motif made up of three intertwined disulfide bridges is a unique feature of several toxins cyclotides and growth factors and occurs in a variety of species including fungi insects molluscs and mammals. Growth factor molecules containing the cystine-knot motif serve as ligands for a diverse range of receptors and play an important role in extracellular signalling. This superfamily of polypeptides comprises several homodimeric and heterodimeric molecules that are central characters in both health and disease. Amongst these molecules are a group of proteins that belong to the vascular endothelial growth factor VEGF subfamily. The members of this family are known angiogenic factors that regulate processes leading to blood vessel formation in physiological and pathological conditions. The focus of the present review is on the structural characteristics of proteins that belong to the VEGF family and on signal-transduction pathways that become initiated via the VEGF receptors. Received 18 May 2011 revised 2 September 2011 accepted 7 September 2011 doi Introduction Disulfide bonds between pairs of cysteine residues in some proteins form a unique functional signature and are considered to