PMID: 16203964

 

    Legend: Gene, Sites

Title : The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand

Abstract :

1. 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 )
2. 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
3. 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
4. This structure completes the gallery of unliganded ErbB receptors and demonstrates that all human ligand-binding ErbBs adopt the autoinhibited conformation
5. 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
6. 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

Output (sent_index, trigger, protein, sugar, site):

• 4. receptors, , ErbB receptors, the gallery, -

Output(Part-Of) (sent_index, protein, site):

• 0. ErbB4, region
• 3. ErbB4, region

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
ErbB1	1956	1,3,5
ErbB4	2066	0,1,3,5
EGFR	1956	1
ErbB	1956	1,2
ErbB receptors	1956	4
epidermal growth factor receptor	1956	1
ErbB receptor	1956	6
HER1	1956	1
HER4	2066	1