2M59
Spatial structure of dimeric VEGFR2 membrane domain in DPC micelles
Summary for 2M59
| Entry DOI | 10.2210/pdb2m59/pdb |
| NMR Information | BMRB: 19041 |
| Descriptor | Vascular endothelial growth factor receptor 2 (1 entity in total) |
| Functional Keywords | vegfr2, receptor tyrosine kinase, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cell junction . Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted . Isoform 3: Secreted: P35968 |
| Total number of polymer chains | 2 |
| Total formula weight | 8262.13 |
| Authors | Mineev, K.S.,Arseniev, A.S.,Shulepko, M.A.,Lyukmanova, E.N. (deposition date: 2013-02-19, release date: 2014-03-12, Last modification date: 2024-05-15) |
| Primary citation | Manni, S.,Mineev, K.S.,Usmanova, D.,Lyukmanova, E.N.,Shulepko, M.A.,Kirpichnikov, M.P.,Winter, J.,Matkovic, M.,Deupi, X.,Arseniev, A.S.,Ballmer-Hofer, K. Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation. Structure, 22:1077-1089, 2014 Cited by PubMed Abstract: Transmembrane signaling by receptor tyrosine kinases (RTKs) entails ligand-mediated dimerization and structural rearrangement of the extracellular domains. RTK activation also depends on the specific orientation of the transmembrane domain (TMD) helices, as suggested by pathogenic, constitutively active RTK mutants. Such mutant TMDs carry polar amino acids promoting stable transmembrane helix dimerization, which is essential for kinase activation. We investigated the effect of polar amino acids introduced into the TMD of vascular endothelial growth factor receptor 2, regulating blood vessel homeostasis. Two mutants showed constitutive kinase activity, suggesting that precise TMD orientation is mandatory for kinase activation. Nuclear magnetic resonance spectroscopy revealed that TMD helices in activated constructs were rotated by 180° relative to the interface of the wild-type conformation, confirming that ligand-mediated receptor activation indeed results from transmembrane helix rearrangement. A molecular dynamics simulation confirmed the transmembrane helix arrangement of wild-type and mutant TMDs revealed by nuclear magnetic resonance spectroscopy. PubMed: 24980797DOI: 10.1016/j.str.2014.05.010 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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