5T89

Crystal structure of VEGF-A in complex with VEGFR-1 domains D1-6

5T89 の概要

• エントリーDOI: 10.2210/pdb5t89/pdb
• 分子名称: Vascular endothelial growth factor A, Vascular endothelial growth factor receptor 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: receptor tyrosine kinase, growth factor, immunoglobulin domain, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 182190.52

構造登録者

Markovic-Mueller, S.,Stuttfeld, E.,Asthana, M.,Weinert, T.,Bliven, S.,Goldie, K.N.,Kisko, K.,Capitani, G.,Ballmer-Hofer, K. (登録日: 2016-09-07, 公開日: 2017-02-01, 最終更新日: 2025-10-01)

主引用文献

Markovic-Mueller, S.,Stuttfeld, E.,Asthana, M.,Weinert, T.,Bliven, S.,Goldie, K.N.,Kisko, K.,Capitani, G.,Ballmer-Hofer, K.
Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A.
Structure, 25:341-352, 2017

PubMed Abstract: Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel development upon activation of three receptor tyrosine kinases: VEGFR-1, -2, and -3. Partial structures of VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, and X-ray crystallography revealed the location of VEGF binding and domain arrangement of individual receptor subdomains. Here, we describe the structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution. We combined X-ray crystallography, single-particle electron microscopy, and molecular modeling for structure determination and validation. The structure reveals the molecular details of ligand-induced receptor dimerization, in particular of homotypic receptor interactions in immunoglobulin homology domains 4, 5, and 7. Functional analyses of ligand binding and receptor activation confirm the relevance of these homotypic contacts and identify them as potential therapeutic sites to allosterically inhibit VEGFR-1 activity.

PubMed: 28111021
DOI: 10.1016/j.str.2016.12.012

実験手法

X-RAY DIFFRACTION (4 Å)