2M20

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

2M20 の概要

• エントリーDOI: 10.2210/pdb2m20/pdb
• NMR情報: BMRB: 18888
• 分子名称: Epidermal growth factor receptor (1 entity in total)
• 機能のキーワード: transmembrane, cell signaling, juxtamembrane, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 13558.50

構造登録者

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. (登録日: 2012-12-11, 公開日: 2013-02-20, 最終更新日: 2024-05-01)

主引用文献

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

実験手法

SOLUTION NMR