2AEW

A model for growth hormone receptor activation based on subunit rotation within a receptor dimer

2AEW の概要

• エントリーDOI: 10.2210/pdb2aew/pdb
• 分子名称: Growth hormone receptor (2 entities in total)
• 機能のキーワード: hormone/growth factor, hormone-growth factor complex
• 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: Cell membrane; Single-pass type I membrane protein. Growth hormone-binding protein: Secreted: P10912
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47901.80

構造登録者

Adams, J.J.,McKinstry, W.J.,Parker, M.W.,Waters, M.J. (登録日: 2005-07-24, 公開日: 2005-11-01, 最終更新日: 2024-11-20)

主引用文献

Brown, R.J.,Adams, J.J.,Pelekanos, R.A.,Wan, Y.,McKinstry, W.J.,Palethorpe, K.,Seeber, R.M.,Monks, T.A.,Eidne, K.A.,Parker, M.W.,Waters, M.J.
Model for growth hormone receptor activation based on subunit rotation within a receptor dimer.
Nat.Struct.Mol.Biol., 12:814-821, 2005

PubMed Abstract: Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.

PubMed: 16116438
DOI: 10.1038/nsmb977

実験手法

X-RAY DIFFRACTION (2.7 Å)