5WNO

Crystal structure of C. elegans LET-23 kinase domain complexed with AMP-PNP

5WNO の概要

• エントリーDOI: 10.2210/pdb5wno/pdb
• 分子名称: Receptor tyrosine-protein kinase let-23, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: receptor tyrosine-protein kinase, dimerization, inactive conformation, cell signaling, let-23, c. elegans, transferase
• 由来する生物種: Caenorhabditis elegans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38480.11

構造登録者

Liu, L.,Thaker, T.M.,Jura, N. (登録日: 2017-08-01, 公開日: 2018-01-31, 最終更新日: 2024-12-25)

主引用文献

Liu, L.,Thaker, T.M.,Freed, D.M.,Frazier, N.,Malhotra, K.,Lemmon, M.A.,Jura, N.
Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23.
Structure, 26:270-281.e4, 2018

PubMed Abstract: In the active HER receptor dimers, kinases play distinct roles; one is the catalytically active kinase and the other is its allosteric activator. This specialization enables signaling by the catalytically inactive HER3, which functions exclusively as an allosteric activator upon heterodimerization with other HER receptors. It is unclear whether the allosteric activation mechanism evolved before HER receptors functionally specialized. We determined the crystal structure of the kinase domain of the only EGF receptor in Caenorhabditis elegans, LET-23. Our structure of a non-human EGFR kinase reveals autoinhibitory features conserved in the human counterpart. Strikingly, mutations within the putative allosteric dimer interface abrogate activity of the isolated LET-23 kinase and of the full-length receptor despite these regions being only partially conserved with human EGFR. Our results indicate that ancestral EGFRs have built-in features that poise them for allosteric activation that could facilitate emergence of the catalytically dead, yet functional, orthologs.

PubMed: 29358026
DOI: 10.1016/j.str.2017.12.012

実験手法

X-RAY DIFFRACTION (2.386 Å)