Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.
Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans.
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DOI：
10.1038/s41467-023-41862-x
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发表时间：
2023-10-07
影响因子：
16.6
通讯作者：
Brzozowski, Andrzej M.
中科院分区：
文献类型：
--
作者：
Viola, Cristina M.;Frittmann, Orsolya;Jenkins, Huw T.;Shafi, Talha;De Meyts, Pierre;Brzozowski, Andrzej M.
胰岛素相关激素通过进化上保守的胰岛素信号轴（IIS）调节后生动物从代谢到生长、寿命和衰老的关键生命过程。在人类中，IIS轴由胰岛素、两种胰岛素样生长因子、胰岛素受体的两种亚型（hIR-A和-B）及其同源IGF-1 R控制。在果蝇中，这种信号传导涉及七种胰岛素样激素（DILP 1 -7）和一种受体（dmIR）。本报告描述了dmIR胞外域：DILP 5复合物的cryoEM结构，揭示了dmIR和hIR之间的高度结构同源性。过量的DILP 5产生呈不对称“T”构象的dmIR复合物，类似于在人IR的一些复合物中观察到的。然而，dmIR以不同的排列结合三个DILP 5分子，也显示出dmIR特异性特征。这项工作增加了结构支持进化保守的IIS轴在IR水平，也巩固了一个重要的模式生物更好地了解。胰岛素激素及其受体调节动物的关键生命过程：从新陈代谢到寿命。人胰岛素受体已被广泛研究。在这里，作者展示了果蝇和人类胰岛素受体的显着结构相似性，表明它们具有普遍的功能。
The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR). This report describes the cryoEM structure of the dmIR ectodomain:DILP5 complex, revealing high structural homology between dmIR and hIR. The excess of DILP5 yields dmIR complex in an asymmetric ‘T’ conformation, similar to that observed in some complexes of human IRs. However, dmIR binds three DILP5 molecules in a distinct arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, and also underpins a better understanding of an important model organism. Insulin hormones and their receptors regulate key life processes in animals: from metabolism to life span. Human insulin receptor has been studied extensively. Here, the authors show remarkable structural similarity of fruit fly and human insulin receptors, indicating their universal functioning.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
DOI：
10.1083/jcb.201711047
发表时间：
2018-05-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gutmann T;Kim KH;Grzybek M;Walz T;Coskun Ü
通讯作者：
Coskun Ü
影响因子：
9.2
作者：
Brogiolo, W;Stocker, H;Hafen, E
通讯作者：
Hafen, E
影响因子：
48
作者：
Bepler, Tristan;Morin, Andrew;Berger, Bonnie
通讯作者：
Berger, Bonnie
DOI：
10.1016/s0006-291x(73)80072-5
发表时间：
1973-01-01
影响因子：
3.1
作者：
DEMEYTS, P;ROTH, J;LESNIAK, MA
通讯作者：
LESNIAK, MA