7F91

SeMet derivative of Thrombocorticin

7F91 の概要

• エントリーDOI: 10.2210/pdb7f91/pdb
• 分子名称: Thrombocorticin (2 entities in total)
• 機能のキーワード: bioactive protein, thrombocorticin, sugar binding protein
• 由来する生物種: Corticium sp. (in: Fungi)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29927.87

構造登録者

Kageyama, H.,Onodera, K.,Sakai, R.,Tanaka, Y. (登録日: 2021-07-03, 公開日: 2022-07-06, 最終更新日: 2024-11-06)

主引用文献

Watari, H.,Kageyama, H.,Masubuchi, N.,Nakajima, H.,Onodera, K.,Focia, P.J.,Oshiro, T.,Matsui, T.,Kodera, Y.,Ogawa, T.,Yokoyama, T.,Hirayama, M.,Hori, K.,Freymann, D.M.,Imai, M.,Komatsu, N.,Araki, M.,Tanaka, Y.,Sakai, R.
A marine sponge-derived lectin reveals hidden pathway for thrombopoietin receptor activation.
Nat Commun, 13:7262-7262, 2022

PubMed Abstract: N-glycan-mediated activation of the thrombopoietin receptor (MPL) under pathological conditions has been implicated in myeloproliferative neoplasms induced by mutant calreticulin, which forms an endogenous receptor-agonist complex that traffics to the cell surface and constitutively activates the receptor. However, the molecular basis for this mechanism is elusive because oncogenic activation occurs only in the cell-intrinsic complex and is thus cannot be replicated with external agonists. Here, we describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. In-depth characterization of lectin-induced activation showed that, similar to oncogenic activation, sugar chain-mediated activation persists due to limited receptor internalization. The strong synergy between ThC and thrombopoietin suggests that ThC catalyzes the formation of receptor dimers on the cell surface. Overall, the existence of sugar-mediated MPL activation, in which the mode of activation is different from the original ligand, suggests that receptor activation is unpredictably diverse in living organisms.

PubMed: 36433967
DOI: 10.1038/s41467-022-34921-2

実験手法

X-RAY DIFFRACTION (1.401 Å)