2M20

EGFR transmembrane - juxtamembrane (TM-JM) segment in bicelles: MD guided NMR refined structure.

Summary for 2M20

• Entry DOI: 10.2210/pdb2m20/pdb
• NMR Information: BMRB: 18888
• Descriptor: Epidermal growth factor receptor (1 entity in total)
• Functional Keywords: transmembrane, cell signaling, juxtamembrane, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• Total number of polymer chains: 2
• Total formula weight: 13558.50

Authors

Endres, N.F.,Das, R.,Smith, A.,Arkhipov, A.,Kovacs, E.,Huang, Y.,Pelton, J.G.,Shan, Y.,Shaw, D.E.,Wemmer, D.E.,Groves, J.T.,Kuriyan, J. (deposition date: 2012-12-11, release date: 2013-02-20, Last modification date: 2024-05-01)

Primary citation

Endres, N.F.,Das, R.,Smith, A.W.,Arkhipov, A.,Kovacs, E.,Huang, Y.,Pelton, J.G.,Shan, Y.,Shaw, D.E.,Wemmer, D.E.,Groves, J.T.,Kuriyan, J.
Conformational Coupling across the Plasma Membrane in Activation of the EGF Receptor.
Cell(Cambridge,Mass.), 152:543-556, 2013

PubMed Abstract: How the epidermal growth factor receptor (EGFR) activates is incompletely understood. The intracellular portion of the receptor is intrinsically active in solution, and to study its regulation, we measured autophosphorylation as a function of EGFR surface density in cells. Without EGF, intact EGFR escapes inhibition only at high surface densities. Although the transmembrane helix and the intracellular module together suffice for constitutive activity even at low densities, the intracellular module is inactivated when tethered on its own to the plasma membrane, and fluorescence cross-correlation shows that it fails to dimerize. NMR and functional data indicate that activation requires an N-terminal interaction between the transmembrane helices, which promotes an antiparallel interaction between juxtamembrane segments and release of inhibition by the membrane. We conclude that EGF binding removes steric constraints in the extracellular module, promoting activation through N-terminal association of the transmembrane helices.

PubMed: 23374349
DOI: 10.1016/j.cell.2012.12.032

Experimental method

SOLUTION NMR