2AHX: Crystal structure of ErbB4/HER4 extracellular domain

Citation:
Abstract
The human ErbB family of receptor tyrosine kinases comprises the epidermal growth factor receptor (EGFR/ErbB1/HER1), ErbB2 (HER2/Neu), ErbB3 (HER3), and ErbB4 (HER4). ErbBs play fundamental roles in cell growth and differentiation events in embryonic and adult tissues, and inappropriate ErbB activity has been implicated in several human cancers. We report here the 2.4 A crystal structure of the extracellular region of human ErbB4 in the absence of ligand and show that it adopts a tethered conformation similar to inactive forms of ErbB1 and ErbB3. This structure completes the gallery of unliganded ErbB receptors and demonstrates that all human ligand-binding ErbBs adopt the autoinhibited conformation. We also show that the binding of neuregulin-1beta to ErbB4 and ErbB3 and the binding of betacellulin to both ErbB4 and ErbB1 does not decrease at low pH, unlike the binding of epidermal growth factor and transforming growth factor-alpha to ErbB1. These results indicate an important role for ligand in determining pH-dependent binding and may explain different responses observed when the same ErbB receptor is stimulated by different ligands.
PDB ID: 2AHXDownload
MMDB ID: 35210
PDB Deposition Date: 2005/7/28
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.396  Å
Source Organism:
Similar Structures:
Biological Unit for 2AHX: monomeric; determined by author and by software (PISA)
Molecular Components in 2AHX
Label Count Molecule
Protein (1 molecule)
1
Receptor Tyrosine-protein Kinase Erbb-4(Gene symbol: ERBB4)
Molecule annotation
Chemicals (9 molecules)
1
5
2
3
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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