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Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY
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...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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American Society for Biochemistry and Molecular Biology
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911289/ https://www.ncbi.nlm.nih.gov/pubmed/20501651 http://dx.doi.org/10.1074/jbc.M110.130658 |
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author | Iyer, Shalini Darley, Paula I. Acharya, K. Ravi |
author_facet | Iyer, Shalini Darley, Paula I. Acharya, K. Ravi |
author_sort | Iyer, Shalini |
collection | PubMed |
description | 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 Å 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. |
format | Text |
id | pubmed-2911289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-29112892010-08-03 Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY Iyer, Shalini Darley, Paula I. Acharya, K. Ravi J Biol Chem Protein Structure and Folding 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 Å 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. American Society for Biochemistry and Molecular Biology 2010-07-30 2010-05-25 /pmc/articles/PMC2911289/ /pubmed/20501651 http://dx.doi.org/10.1074/jbc.M110.130658 Text en © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles |
spellingShingle | Protein Structure and Folding Iyer, Shalini Darley, Paula I. Acharya, K. Ravi Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY |
title | Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY |
title_full | Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY |
title_fullStr | Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY |
title_full_unstemmed | Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY |
title_short | Structural Insights into the Binding of Vascular Endothelial Growth Factor-B by VEGFR-1(D2): RECOGNITION AND SPECIFICITY |
title_sort | structural insights into the binding of vascular endothelial growth factor-b by vegfr-1(d2): recognition and specificity |
topic | Protein Structure and Folding |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911289/ https://www.ncbi.nlm.nih.gov/pubmed/20501651 http://dx.doi.org/10.1074/jbc.M110.130658 |
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