4GT4

Structure of unliganded, inactive Ror2 kinase domain

4GT4 の概要

• エントリーDOI: 10.2210/pdb4gt4/pdb
• 関連するPDBエントリー: 4GT5
• 分子名称: Tyrosine-protein kinase transmembrane receptor ROR2, NITRATE ION (3 entities in total)
• 機能のキーワード: atp binding, phosphorylation, membrane, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: Q01974
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 71175.47

構造登録者

Mendrola, J.M.,Lemmon, M.A. (登録日: 2012-08-28, 公開日: 2012-09-26, 最終更新日: 2024-11-20)

主引用文献

Artim, S.C.,Mendrola, J.M.,Lemmon, M.A.
Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family.
Biochem.J., 448:213-220, 2012

PubMed Abstract: To investigate the range of autoinhibitory mechanisms used by TKDs (tyrosine kinase domains) from the insulin receptor family of RTKs (receptor tyrosine kinases), we determined crystal structures of TKDs from TrkA (tropomyosin receptor kinase A, a nerve growth factor receptor) and Ror2 (receptor tyrosine kinase-like orphan receptor 2, an unconventional Wnt receptor). TrkA autoinhibition closely resembles that seen for the insulin receptor, relying on projection of an activation loop tyrosine residue into the substrate-binding site and occlusion of the ATP-binding site by the activation loop. Ror2 employs similar mechanisms, but the unusual replacement of the phenylalanine residue in its Asp-Phe-Gly motif with leucine necessitates occlusion of the ATP-binding site by other means. The unusual Asp-Leu-Gly motif in Ror2 is displaced compared with other inactive kinases, allowing the activation loop to interact directly with the TKD's αC helix, in another mode of autoinhibition that is characteristic of the other extreme of this receptor family: ALK (anaplastic lymphoma kinase) and Met. These findings provide insight into the expected range of activating mutations in these TKDs in cancer. We also describe symmetrical dimers of the inactive TrkA TKD resembling those found in other RTKs, possibly reflecting an arrangement of kinase domains in a pre-formed TrkA dimer.

PubMed: 22992069
DOI: 10.1042/BJ20121365

実験手法

X-RAY DIFFRACTION (2.406 Å)