7KJC

Crystal structure of the EphA2 S901E mutant intracellular KD-SAM domains

7KJC の概要

• エントリーDOI: 10.2210/pdb7kjc/pdb
• 分子名称: Ephrin type-A receptor 2, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: eph receptor, kinase, sam, allostery, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 89404.41

構造登録者

Lechtenberg, B.C.,Pasquale, E.B. (登録日: 2020-10-26, 公開日: 2021-02-03, 最終更新日: 2023-10-18)

主引用文献

Lechtenberg, B.C.,Gehring, M.P.,Light, T.P.,Horne, C.R.,Matsumoto, M.W.,Hristova, K.,Pasquale, E.B.
Regulation of the EphA2 receptor intracellular region by phosphomimetic negative charges in the kinase-SAM linker.
Nat Commun, 12:7047-7047, 2021

PubMed Abstract: Eph receptor tyrosine kinases play a key role in cell-cell communication. Lack of structural information on the entire multi-domain intracellular region of any Eph receptor has hindered understanding of their signaling mechanisms. Here, we use integrative structural biology to investigate the structure and dynamics of the EphA2 intracellular region. EphA2 promotes cancer malignancy through a poorly understood non-canonical form of signaling involving serine/threonine phosphorylation of the linker connecting its kinase and SAM domains. We show that accumulation of multiple linker negative charges, mimicking phosphorylation, induces cooperative changes in the EphA2 intracellular region from more closed to more extended conformations and perturbs the EphA2 juxtamembrane segment and kinase domain. In cells, linker negative charges promote EphA2 oligomerization. We also identify multiple kinases catalyzing linker phosphorylation. Our findings suggest multiple effects of linker phosphorylation on EphA2 signaling and imply that coordination of different kinases is necessary to promote EphA2 non-canonical signaling.

PubMed: 34857764
DOI: 10.1038/s41467-021-27343-z

実験手法

X-RAY DIFFRACTION (2.3 Å)