2M59

Spatial structure of dimeric VEGFR2 membrane domain in DPC micelles


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: target function 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural and functional characterization of alternative transmembrane domain conformations in VEGF receptor 2 activation.

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.

(2014) Structure 22: 1077-1089

  • DOI: https://doi.org/10.1016/j.str.2014.05.010
  • Primary Citation of Related Structures:  
    2M59, 2MET, 2MEU

  • 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.


  • Organizational Affiliation

    Paul Scherrer Institute, Biomolecular Research, 5232 Villigen PSI, Switzerland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vascular endothelial growth factor receptor 2
A, B
37Homo sapiensMutation(s): 0 
Gene Names: KDRFLK1VEGFR2
EC: 2.7.10.1
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P35968 (Homo sapiens)
Explore P35968 
Go to UniProtKB:  P35968
PHAROS:  P35968
GTEx:  ENSG00000128052 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35968
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 10 
  • Selection Criteria: target function 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-03-12
    Type: Initial release
  • Version 1.1: 2017-09-06
    Changes: Database references
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Other
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references