Hidden pathway for cytokine receptor activation: Structural insights into a marine sponge-derived lectin that activates the thrombopoietin receptor via recognition of the fucose moiety
Hidden pathway for cytokine receptor activation: Structural insights into a marine sponge-derived lectin that activates the thrombopoietin receptor via recognition of the fucose moiety
复制标题
细胞因子受体激活的隐藏途径：对海绵来源的凝集素的结构见解，该凝集素通过识别岩藻糖部分来激活血小板生成素受体
DOI：
10.1101/2021.10.29.466502
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Tanaka Yoshikazu
中科院分区：
文献类型：
--
作者：
Watari Hiromi;Kageyama Hiromu;Masubuchi Nami;Nakajima Hiroya;Onodera Kako;Focia Pamela J.;Oshiro Takumi;Matsui Takashi;Kodera Yoshio;Ogawa Tomohisa;Yokoyama Takeshi;Hirayama Makoto;Hori Kanji;Freymann Douglas M.;Komatsu Norio;Araki Marito;Tanaka Yoshikazu
在病理条件下，N-聚糖介导的血小板生成素受体（MPL）活化与突变钙网蛋白诱导的骨髓增生性肿瘤有关，突变钙网蛋白形成内源性受体-激动剂复合物，组成性激活受体。然而，这种机制的分子基础尚未研究，因为没有外部激动剂存在。我们描述的结构和功能的海洋海绵衍生的MPL激动剂，血小板皮质素（ThC），同源二聚凝集素与钙依赖性岩藻糖结合特性。ThC诱导的激活由于有限的受体内化而持续。ThC和血小板生成素之间的强协同作用表明ThC催化细胞表面上受体二聚体的形成。MPL受糖介导的活化，其中动力学不同于细胞因子。这一结果表明存在不同的受体激活途径在人类thromboiesis.One-sentence summaryA海洋海绵凝集素催化血小板生成素受体二聚化和激活，表现出很强的协同作用与血小板生成素，并调节受体的内化。
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 constitutively activates the receptor. However, the molecular basis for this mechanism has not been studied because no external agonists existed. We describe the structure and function of a marine sponge-derived MPL agonist, thrombocorticin (ThC), a homodimerized lectin with calcium-dependent fucose-binding properties. ThC-induced 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. MPL is subject to sugar-mediated activation, where the kinetics differ from those of cytokines. This result suggests the presence of diverse receptor activation pathways in human thrombopoiesis.One-sentence summaryA marine sponge lectin catalyzes thrombopoietin receptor dimerization and activation, exhibiting strong synergy with thrombopoietin, and modulates internalization of the receptor.
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影响因子：
28.2
作者：
Elf S;Abdelfattah NS;Chen E;Perales-Patón J;Rosen EA;Ko A;Peisker F;Florescu N;Giannini S;Wolach O;Morgan EA;Tothova Z;Losman JA;Schneider RK;Al-Shahrour F;Mullally A
通讯作者：
Mullally A
慢性骨髓增生性肿瘤 突变型钙网蛋白与分泌途径中的 MPL 相互作用，在细胞表面激活
DOI：
--
发表时间：
2019
期刊：
影响因子：
--
作者：
Nami Masubuchi;Marito Araki;Yinjie Yang;Erina Hayashi;M. Imai;Y. Edahiro;Yumi Hironaka;Yoshihisa Mizukami;Yoshihiko Kihara;Hiraku Takei;Mai Nudejima;M. Koike;A. Ohsaka;N. Komatsu
通讯作者：
N. Komatsu
影响因子：
3.3
作者：
Hitchcock IS;Hafer M;Sangkhae V;Tucker JA
通讯作者：
Tucker JA
影响因子：
3.5
作者：
Sabin, C;Mitchell, EP;Imberty, A
通讯作者：
Imberty, A
影响因子：
8.6
作者：
Kizuka, Yasuhiko;Nakano, Miyako;Taniguchi, Naoyuki
通讯作者：
Taniguchi, Naoyuki