2M0B

Homodimeric transmembrane domain of the human receptor tyrosine kinase ErbB1 (EGFR, HER1) in micelles

Summary for 2M0B

• Entry DOI: 10.2210/pdb2m0b/pdb
• NMR Information: BMRB: 18804
• Descriptor: Epidermal growth factor receptor (1 entity in total)
• Functional Keywords: transmembrane domain, erbb1, receptor, dimerization, tyrosine kinase, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 9467.70

Authors

Lesovoy, D.M.,Bocharov, E.V.,Pustovalova, Y.E.,Bocharova, O.V.,Arseniev, A.S. (deposition date: 2012-10-24, release date: 2013-10-30, Last modification date: 2024-05-01)

Primary citation

Bocharov, E.V.,Lesovoy, D.M.,Pavlov, K.V.,Pustovalova, Y.E.,Bocharova, O.V.,Arseniev, A.S.
Alternative packing of EGFR transmembrane domain suggests that protein-lipid interactions underlie signal conduction across membrane.
Biochim. Biophys. Acta, 1858:1254-1261, 2016

PubMed Abstract: The human epidermal growth factor receptor (EGFR) of HER/ErbB receptor tyrosine kinase family mediates a broad spectrum of cellular responses transducing biochemical signals via lateral dimerization in plasma membrane, while inactive receptors can exist in both monomeric and dimeric forms. Recently, the dimeric conformation of the helical single-span transmembrane domains of HER/ErbB employing the relatively polar N-terminal motifs in a fashion permitting proper kinase activation was experimentally determined. Here we describe the EGFR transmembrane domain dimerization via an alternative weakly polar C-terminal motif A(661)xxxG(665) presumably corresponding to the inactive receptor state. During association, the EGFR transmembrane helices undergo a structural adjustment with adaptation of inter-molecular polar and hydrophobic interactions depending upon the surrounding membrane properties that directly affect the transmembrane helix packing. This might imply that signal transduction through membrane and allosteric regulation are inclusively mediated by coupled protein-protein and protein-lipid interactions, elucidating paradoxically loose linkage between ligand binding and kinase activation.

PubMed: 26903218
DOI: 10.1016/j.bbamem.2016.02.023

Experimental method

SOLUTION NMR