3U7U

Crystal structure of extracellular region of human epidermal growth factor receptor 4 in complex with neuregulin-1 beta

Summary for 3U7U

• Entry DOI: 10.2210/pdb3u7u/pdb
• Descriptor: Receptor tyrosine-protein kinase erbB-4, Neuregulin 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: signaling protein, transferase-transferase regulator complex, glycosylation, transferase/transferase regulator
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 455341.19

Authors

Liu, P.,Cleveland IV, T.E.,Bouyain, S.,Longo, P.A.,Leahy, D.J. (deposition date: 2011-10-14, release date: 2012-08-29, Last modification date: 2024-11-27)

Primary citation

Liu, P.,Cleveland, T.E.,Bouyain, S.,Byrne, P.O.,Longo, P.A.,Leahy, D.J.
A single ligand is sufficient to activate EGFR dimers.
Proc.Natl.Acad.Sci.USA, 109:10861-10866, 2012

PubMed Abstract: Crystal structures of human epidermal growth factor receptor (EGFR) with bound ligand revealed symmetric, doubly ligated receptor dimers thought to represent physiologically active states. Such complexes fail to rationalize negative cooperativity of epidermal growth factor (EGF) binding to EGFR and the behavior of the ligandless EGFR homolog ErbB2/HER2, however. We report cell-based assays that provide evidence for active, singly ligated dimers of human EGFR and its homolog, ErbB4/HER4. We also report crystal structures of the ErbB4/HER4 extracellular region complexed with its ligand Neuregulin-1β that resolve two types of ErbB dimer when compared to EGFR:Ligand complexes. One type resembles the recently reported asymmetric dimer of Drosophila EGFR with a single high-affinity ligand bound and provides a model for singly ligated human ErbB dimers. These results unify models of vertebrate and invertebrate EGFR/ErbB signaling, imply that the tethered conformation of unliganded ErbBs evolved to prevent crosstalk among ErbBs, and establish a molecular basis for both negative cooperativity of ligand binding to vertebrate ErbBs and the absence of active ErbB2/HER2 homodimers in normal conditions.

PubMed: 22699492
DOI: 10.1073/pnas.1201114109

Experimental method

X-RAY DIFFRACTION (3.03 Å)