Modelling the structure of Short Gastrulation and generation of a toolkit for studying its function in Drosophila.
Modelling the structure of Short Gastrulation and generation of a toolkit for studying its function in Drosophila.
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作者：
BMP梯度对于无脊椎动物和脊椎动物胚胎的背腹轴图案化是必不可少的。果蝇细胞外BMP结合蛋白短胃化（Sog）在BMP梯度形成中起关键作用。在本研究中，我们将联合收割机结合基因组编辑、结构和发育方法来研究果蝇中Sog的功能。我们产生了一个sog敲除苍蝇股票，它允许简单的重组sog编码序列的改变版本。作为原理证明，我们测试了对两个半胱氨酸残基的要求，这两个半胱氨酸残基先前被确定为棕榈酰化的靶点，棕榈酰化被提出来增强Sog分泌。然而，我们表明，sogC 27，28 S突变体是可行的，只有非常温和的表型，表明这些残基和它们的潜在的修改是不重要的Sog分泌在体内。此外，我们使用实验负染色EM成像和流体动力学数据来验证Sog的AlphaFold结构预测。该模型表明一个更紧凑的形状比脊椎动物的直系同源物Chordin和C-末端冯维勒布兰德C域之间的构象灵活性。我们讨论了如何改变这种紧凑性可能有助于在BMP梯度形成过程中的Sog和Chordin功能的机械差异。.总结：作者模拟了Sog的结构，并建立了一种新的sog敲除果蝇种群，他们验证了特定sog突变的测试。
A BMP gradient is essential for patterning the dorsal-ventral axis of invertebrate and vertebrate embryos. The extracellular BMP binding protein Short Gastrulation (Sog) in Drosophila plays a key role in BMP gradient formation. In this study, we combine genome editing, structural and developmental approaches to study Sog function in Drosophila. We generate a sog knockout fly stock, which allows simple reintegration of altered versions of the sog coding sequence. As proof-of-principle, we test the requirement for two cysteine residues that were previously identified as targets for palmitoylation, which has been proposed to enhance Sog secretion. However, we show that the sogC27,28S mutant is viable with only very mild phenotypes, indicating that these residues and their potential modification are not critical for Sog secretion in vivo. Additionally, we use experimental negative stain EM imaging and hydrodynamic data to validate the AlphaFold structure prediction for Sog. The model suggests a more compact shape than the vertebrate ortholog Chordin and conformational flexibility between the C-terminal von Willebrand C domains. We discuss how this altered compactness may contribute to mechanistic differences in Sog and Chordin function during BMP gradient formation. . Summary: The authors model the structure of Sog and establish a new sog knockout fly stock that they validate for the testing of specific sog mutations.
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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
影响因子：
5.9
作者：
Calvo L;Ronshaugen M;Pettini T
通讯作者：
Pettini T
影响因子：
5.8
作者：
Bandyopadhyay, Amitabha;Yadav, Prem Swaroop;Prashar, Paritosh
通讯作者：
Prashar, Paritosh
影响因子：
64.8
作者：
Ashe, HL;Levine, M
通讯作者：
Levine, M
影响因子：
10.5
作者：
FRANCOIS, V;SOLLOWAY, M;BIER, E
通讯作者：
BIER, E