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Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity.

Iyer S, Darley PI, Acharya KR
J Biol Chem 285 23779-89 (2010)
Cited: 36 times
EuropePMC logo PMID: 20501651

Abstract

The formation of blood vessels (angiogenesis) is a highly orchestrated sequence of events involving crucial receptor-ligand interactions. Angiogenesis is critical for physiological processes such as development, wound healing, reproduction, tissue regeneration, and remodeling. It also plays a major role in sustaining tumor progression and chronic inflammation. Vascular endothelial growth factor (VEGF)-B, a member of the VEGF family of angiogenic growth factors, effects blood vessel formation by binding to a tyrosine kinase receptor, VEGFR-1. There is growing evidence of the important role played by VEGF-B in physiological and pathological vasculogenesis. Development of VEGF-B antagonists, which inhibit the interaction of this molecule with its cognate receptor, would be important for the treatment of pathologies associated specifically with this growth factor. In this study, we present the crystal structure of the complex of VEGF-B with domain 2 of VEGFR-1 at 2.7 A resolution. Our analysis reveals that each molecule of the ligand engages two receptor molecules using two symmetrical binding sites. Based on these interactions, we identify the receptor-binding determinants on VEGF-B and shed light on the differences in specificity towards VEGFR-1 among the different VEGF homologs.

Reviews - 2xac mentioned but not cited (4)

  1. Tying the knot: the cystine signature and molecular-recognition processes of the vascular endothelial growth factor family of angiogenic cytokines. Iyer S, Acharya KR. FEBS J 278 4304-4322 (2011)
  2. Positive and Negative Regulation of Angiogenesis by Soluble Vascular Endothelial Growth Factor Receptor-1. Failla CM, Carbo M, Morea V. Int J Mol Sci 19 E1306 (2018)
  3. Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy. Shaik F, Cuthbert GA, Homer-Vanniasinkam S, Muench SP, Ponnambalam S, Harrison MA. Biomolecules 10 1673 (2020)
  4. A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics. Ye X, Gaucher JF, Vidal M, Broussy S. Molecules 26 6759 (2021)

Articles - 2xac mentioned but not cited (9)

  1. Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2): recognition and specificity. Iyer S, Darley PI, Acharya KR. J Biol Chem 285 23779-23789 (2010)
  2. A peptide mimicking the binding sites of VEGF-A and VEGF-B inhibits VEGFR-1/-2 driven angiogenesis, tumor growth and metastasis. Farzaneh Behelgardi M, Zahri S, Mashayekhi F, Mansouri K, Asghari SM. Sci Rep 8 17924 (2018)
  3. A novel peptide specifically binding to VEGF receptor suppresses angiogenesis in vitro and in vivo. Zhang Y, He B, Liu K, Ning L, Luo D, Xu K, Zhu W, Wu Z, Huang J, Xu X. Signal Transduct Target Ther 2 17010 (2017)
  4. Letter Molecular docking, synthesis and biological evaluation of Vascular Endothelial Growth Factor (VEGF) B based peptide as antiangiogenic agent targeting the second domain of the Vascular Endothelial Growth Factor Receptor 1 (VEGFR1D2) for anticancer application. Sadremomtaz A, Ali AM, Jouyandeh F, Balalaie S, Navari R, Broussy S, Mansouri K, Groves MR, Asghari SM. Signal Transduct Target Ther 5 76 (2020)
  5. Biophysical Studies of the Induced Dimerization of Human VEGF Receptor 1 Binding Domain by Divalent Metals Competing with VEGF-A. Gaucher JF, Reille-Seroussi M, Gagey-Eilstein N, Broussy S, Coric P, Seijo B, Lascombe MB, Gautier B, Liu WQ, Huguenot F, Inguimbert N, Bouaziz S, Vidal M, Broutin I. PLoS One 11 e0167755 (2016)
  6. Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents. Dawoud NTA, El-Fakharany EM, Abdallah AE, El-Gendi H, Lotfy DR. Sci Rep 12 3424 (2022)
  7. Rational Design of Antiangiogenic Helical Oligopeptides Targeting the Vascular Endothelial Growth Factor Receptors. Zanella S, Bocchinfuso G, De Zotti M, Arosio D, Marino F, Raniolo S, Pignataro L, Sacco G, Palleschi A, Siano AS, Piarulli U, Belvisi L, Formaggio F, Gennari C, Stella L. Front Chem 7 170 (2019)
  8. A Cyclic Peptide Epitope of an Under-Explored VEGF-B Loop 1 Demonstrated In Vivo Anti-Angiogenic and Anti-Tumor Activities. Wang L, Xu M, Hu H, Zhang L, Ye F, Jin J, Fang H, Chen J, Chen G, Broussy S, Vidal M, Lv Z, Liu WQ. Front Pharmacol 12 734544 (2021)
  9. Structural Studies on an Anti-Angiogenic Peptide Using Molecular Modeling. Assareh E, Mehrnejad F, Asghari SM. Iran J Biotechnol 18 e2553 (2020)


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  3. Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions. Hota PK, Buck M. Cell Mol Life Sci 69 3765-3805 (2012)
  4. Vascular endothelial growth factor-B in physiology and disease. Bry M, Kivelä R, Leppänen VM, Alitalo K. Physiol Rev 94 779-794 (2014)
  5. An assessment of current techniques for inducing axon regeneration and neurological recovery following peripheral nerve trauma. Kuffler DP. Prog Neurobiol 116 1-12 (2014)

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  1. Thermodynamic and structural description of allosterically regulated VEGFR-2 dimerization. Brozzo MS, Bjelić S, Kisko K, Schleier T, Leppänen VM, Alitalo K, Winkler FK, Ballmer-Hofer K. Blood 119 1781-1788 (2012)
  2. Structural and mechanistic insights into VEGF receptor 3 ligand binding and activation. Leppänen VM, Tvorogov D, Kisko K, Prota AE, Jeltsch M, Anisimov A, Markovic-Mueller S, Stuttfeld E, Goldie KN, Ballmer-Hofer K, Alitalo K. Proc Natl Acad Sci U S A 110 12960-12965 (2013)
  3. Structural determinants of vascular endothelial growth factor-D receptor binding and specificity. Leppänen VM, Jeltsch M, Anisimov A, Tvorogov D, Aho K, Kalkkinen N, Toivanen P, Ylä-Herttuala S, Ballmer-Hofer K, Alitalo K. Blood 117 1507-1515 (2011)
  4. Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: a computational approach. Platania CB, Di Paola L, Leggio GM, Romano GL, Drago F, Salomone S, Bucolo C. Front Pharmacol 6 248 (2015)
  5. The basis for the distinct biological activities of vascular endothelial growth factor receptor-1 ligands. Anisimov A, Leppänen VM, Tvorogov D, Zarkada G, Jeltsch M, Holopainen T, Kaijalainen S, Alitalo K. Sci Signal 6 ra52 (2013)
  6. News Structure and function of vascular endothelial growth factor and its receptor system. Park SA, Jeong MS, Ha KT, Jang SB. BMB Rep 51 73-78 (2018)
  7. Both Kdr and Flt1 play a vital role in hypoxia-induced Src-PLD1-PKCγ-cPLA(2) activation and retinal neovascularization. Singh NK, Hansen DE, Kundumani-Sridharan V, Rao GN. Blood 121 1911-1923 (2013)
  8. Evaluation of the growth factors VEGF-a and VEGF-B in the vitreous and serum of patients with macular and retinal vascular diseases. Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, Neves A, Passarinha LA, Tomaz CT. Growth Factors 36 48-57 (2018)
  9. Characterization of a drug-targetable allosteric site regulating vascular endothelial growth factor signaling. Thieltges KM, Avramovic D, Piscitelli CL, Markovic-Mueller S, Binz HK, Ballmer-Hofer K. Angiogenesis 21 533-543 (2018)
  10. Design and synthesis of C-terminal modified cyclic peptides as VEGFR1 antagonists. Wang L, Gagey-Eilstein N, Broussy S, Reille-Seroussi M, Huguenot F, Vidal M, Liu WQ. Molecules 19 15391-15407 (2014)
  11. VEGF-B Levels in the Vitreous of Diabetic and Non-Diabetic Patients with Ocular Diseases and Its Correlation with Structural Parameters. Mesquita J, Castro de Sousa JP, Vaz-Pereira S, Neves A, Tavares-Ratado P, M Santos F, A Passarinha L, T Tomaz C. Med Sci (Basel) 5 E17 (2017)
  12. Functional antibody characterization via direct structural analysis and information-driven protein-protein docking. Depetris RS, Lu D, Polonskaya Z, Zhang Z, Luna X, Tankard A, Kolahi P, Drummond M, Williams C, Ebert MCCJC, Patel JP, Poyurovsky MV. Proteins 90 919-935 (2022)
  13. Short PlGF-derived peptides bind VEGFR-1 and VEGFR-2 in vitro and on the surface of endothelial cells. Caporale A, Martin AD, Capasso D, Focà G, Sandomenico A, D'Andrea LD, Grieco P, Ruvo M, Doti N. J Pept Sci 25 e3146 (2019)
  14. The Evaluation of the Relationship between sTREM-1, VEGF-B, and VEGF Gene Expression Levels with Disease Activity of Behçet's Patients. Harmanci K, Akan OY, Pirildar T, Ortan P, Ulman C. Dis Markers 2018 2649392 (2018)
  15. Investigation of Site-Specific Differences in Glycan Microheterogeneity by N-Glycopeptide Mapping of VEGFR-IgG Fusion Protein. Hahm YH, Lee JY, Ahn YH. Molecules 24 E3924 (2019)
  16. A Three-Dimensional Sensor to Recognize Amyloid-β in Blood Plasma of Patients. Na J, Hwang E, Choi JS, Ji MJ, Noh Y, Lim YB, Choi HJ. ACS Omega 5 27295-27303 (2020)
  17. A VEGFB-Based Peptidomimetic Inhibits VEGFR2-Mediated PI3K/Akt/mTOR and PLCγ/ERK Signaling and Elicits Apoptotic, Antiangiogenic, and Antitumor Activities. Namjoo M, Ghafouri H, Assareh E, Aref AR, Mostafavi E, Hamrahi Mohsen A, Balalaie S, Broussy S, Asghari SM. Pharmaceuticals (Basel) 16 906 (2023)
  18. Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis. Sun D, Guo K, Liu N, Li Y, Li Y, Hu Y, Li S, Fu Z, Wang Y, Wu Y, Zhang Y, Li J, Li C, Wang Z, Kang Z, Sun J, Wang Y, Yang X. Burns Trauma 11 tkad035 (2023)


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