The calcium-binding type III repeats domain of thrombospondin-2 binds to fibroblast growth factor 2 (FGF2)

Angiogenesis
Marco RusnatiGiulia Taraboletti

Abstract

Thrombospondin (TSP)-1 and TSP-2 share similar structures and functions, including a remarkable antiangiogenic activity. We have previously demonstrated that a mechanism of the antiangiogenic activity of TSP-1 is the interaction of its type III repeats domain with fibroblast growth factor-2 (FGF2), affecting the growth factor bioavailability and angiogenic activity. Since the type III repeats domain is conserved in TSP-2, this study aimed at investigating whether also TSP-2 retained the ability to interact with FGF2. The FGF2 binding properties of TSP-1 and TSP-2 and their recombinant domains were analyzed by solid-phase binding and surface plasmon resonance assays. TSP-2 bound FGF2 with high affinity (Kd = 1.3 nM). TSP-2/FGF2 binding was inhibited by calcium and heparin. The FGF2-binding domain of TSP-2 was located in the type III repeats and the minimal interacting sequence was identified as the GVTDEKD peptide in repeat 3C, corresponding to KIPDDRD, the active sequence of TSP-1. A second putative FGF2 binding sequence was also identified in repeat 11C of both TSPs. Computational docking analysis predicted that both the TSP-2 and TSP-1-derived heptapeptides interacted with FGF2 with comparable binding properties. Accordingly,...Continue Reading

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Citations

May 23, 2019·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Joanne E Murphy-Ullrich
Jun 20, 2019·Journal of Cellular Physiology·Xiuling ShangRongguo Yu
Sep 17, 2020·American Journal of Physiology. Cell Physiology·Laura Carminati, Giulia Taraboletti
May 28, 2020·International Journal of Molecular Sciences·Eva AndreuzziMaurizio Mongiat
Dec 3, 2020·Frontiers in Cell and Developmental Biology·Jia Zheng, Chengzhi Lu
Mar 10, 2021·Journal of Receptor and Signal Transduction Research·Yanfang WangFei Dong
May 18, 2021·Frontiers in Molecular Biosciences·Yi LuChujun Li
Oct 4, 2021·Fluids and Barriers of the CNS·Vania SepúlvedaTeresa Caprile
Nov 7, 2020·Current Drug Targets·Hamideh Sadat MohammadipourAli Forouzanfar

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Methods Mentioned

BETA
NMR

Software Mentioned

AA
Glide
Basic Local Alignment Search Tool ( BLAST )
CUDA
LEaP
OPLS
Gromacs

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