Structure of the Extracellular Region of HER3 Reveals an Interdomain Tether

@article{Cho2002StructureOT,
  title={Structure of the Extracellular Region of HER3 Reveals an Interdomain Tether},
  author={Hyun-soo Cho and Daniel J. Leahy},
  journal={Science},
  year={2002},
  volume={297},
  pages={1330 - 1333}
}
We have determined the 2.6 angstrom crystal structure of the entire extracellular region of human HER3 (ErbB3), a member of the epidermal growth factor receptor (EGFR) family. The structure consists of four domains with structural homology to domains found in the type I insulin-like growth factor receptor. The HER3 structure reveals a contact between domains II and IV that constrains the relative orientations of ligand-binding domains and provides a structural basis for understanding both… 
Rigidity of the extracellular part of HER2: Evidence from engineering subdomain interfaces and shared‐helix DARPin‐DARPin fusions
TLDR
The rigidity of HER2 on the surface of tumor cells is demonstrated by employing two orthogonal approaches of protein engineering, which exclude, on live cells and in vitro, that significant proportions of Her2 deviate from the “open” conformation.
A structural perspective on the regulation of the epidermal growth factor receptor.
TLDR
The epidermal growth factor receptor is a receptor tyrosine kinase that plays a critical role in the pathogenesis of many cancers, and its activation mechanism is reviewed here.
Molecular modeling of nearly full-length ErbB2 receptor.
TLDR
Favorable dimerization interactions are predicted for the extracellular, transmembrane, and protein kinase domains in the model of a nearly full-length dimer of ErbB2, which may act in a coordinated fashion in Erb B2 homodimerization, and also in heterodimers of ErBB2 with other members of the ErbA family.
Her2 activation mechanism reflects evolutionary preservation of asymmetric ectodomain dimers in the human EGFR family
TLDR
Results from long-timescale molecular dynamics simulations indicating that a single ligand is necessary and sufficient to stabilize the ectodomain interface of Her2 heterodimers, which assume an asymmetric conformation similar to that of dEGFR dimers suggest a dimerization mechanism that has been conserved in the evolution of the EGFR family from Drosophila to human.
EGFR Receptor Family Extracellular Domain Structures and Functions
TLDR
Surprisingly, when forming the activated, ligand-bound structures, the EGFR, ErbB3 and,ErbB4 undergo major conformational changes.
The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand.
TLDR
An important role for ligand in determining pH-dependent binding is indicated and may explain different responses observed when the same ErbB receptor is stimulated by different ligands.
...
...

References

SHOWING 1-10 OF 31 REFERENCES
Epidermal growth factor binding induces a conformational change in the external domain of its receptor.
TLDR
The ligand additions to the human EGF receptor showed differences in both the near‐ and far‐UV CD spectra, and were similar for each ligand used, suggesting similar conformational differences between uncomplexed and complexed receptor.
Noncontiguous regions in the extracellular domain of EGF receptor define ligand-binding specificity.
TLDR
Analysis of the binding properties of novel chicken/human EGFR chimera to further delineate the contact sequences in domain III and to assess the role of other regions of EGFR for their contribution to the display of high-affinity EGF binding concludes that noncontiguous regions of the EGFR contribute additively to the binding of EGF.
The Single Transmembrane Domains of ErbB Receptors Self-associate in Cell Membranes*
TLDR
A role for TM domain interactions in ErbB receptor function is suggested, possibly in stabilizing inactive ligand-independent receptor dimers that have been observed by several groups.
Dimerization of the Extracellular Domain of the Receptor for Epidermal Growth Factor Containing the Membrane-spanning Segment in Response to Treatment with Epidermal Growth Factor*
TLDR
A recombinant fragment of the human receptor for epidermal growth factor containing both its extracellular domain and its membrane-spanning segment, when dissolved with Triton X-100, was observed to dimerize in response to addition of EGF even at the lowest concentration that could be assayed, suggesting that interfaces between cytoplasmic domains of intact EGF receptor impart significant stabilization to the dimer of the enzyme.
Two EGF molecules contribute additively to stabilization of the EGFR dimer
TLDR
The proposed model of EGF‐induced sEGFR dimerization suggests possible mechanisms for both ligand‐induced homo‐ and heterodimerization of the EGFR (or erbB) family of receptors.
The extracellular domain of the epidermal growth factor receptor. Studies on the affinity and stoichiometry of binding, receptor dimerization and a binding-domain mutant.
TLDR
It is shown, using sedimentation equilibrium analysis, that ligand binding induces significant dimerization of the EGFR extracellular domain, and identified amino acid residues which are close to the binding site since they are common to the epitopes of several ligand-competitive monoclonal antibodies.
Solution structure of murine epidermal growth factor determined by NMR spectroscopy and refined by energy minimization with restraints.
TLDR
The atomic coordinates resulting from the present structure refinement are important data for understanding the structures of EGF-like proteins and for further detailed comparisons of these structures with mEGF.
The ErbB signaling network: receptor heterodimerization in development and cancer
TLDR
The role of ErbB receptors as normal signal transducers and their contribution to the process of malignant transformation during tumor development are concentrated on.
Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells
The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close
...
...