Towards a structurally resolved human protein interaction network.
Towards a structurally resolved human protein interaction network.
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DOI：
10.1038/s41594-022-00910-8
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发表时间：
2023-02
影响因子：
16.8
通讯作者：
Elofsson, Arne
中科院分区：
文献类型：
--
作者：
Burke, David F.;Bryant, Patrick;Barrio-Hernandez, Inigo;Memon, Danish;Pozzati, Gabriele;Shenoy, Aditi;Zhu, Wensi;Dunham, Alistair S.;Albanese, Pascal;Keller, Andrew;Scheltema, Richard A.;Bruce, James E.;Leitner, Alexander;Kundrotas, Petras;Beltrao, Pedro;Elofsson, Arne
细胞功能由分子机器控制，分子机器通过蛋白质-蛋白质相互作用组装。它们的原子细节对于研究它们的分子机制至关重要。然而，在数十万种人类蛋白质相互作用中，只有不到5%的蛋白质具有结构特征。在这里，我们测试了使用AlphaFold 2来预测65，484种人类蛋白质相互作用结构的深度学习方法的潜力和局限性。我们表明，实验可以正交确认更高的置信度模型。我们确定了3,137个高置信度模型，其中1,371个与已知结构没有同源性。我们确定了携带疾病突变的界面残基，提示致病性变异的潜在机制。界面磷酸化位点组显示跨条件的共调节模式，提示作为信号应答的多个蛋白质相互作用的协调调节。最后，我们提供了预测的二元复合物如何用于构建更大的组件的例子，有助于扩大我们对人类细胞生物学的理解。在这里，作者探索了AlphaFold 2预测人类蛋白质-蛋白质相互作用组结构的能力及其局限性。
Cellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details are critical to studying their molecular mechanisms. However, fewer than 5% of hundreds of thousands of human protein interactions have been structurally characterized. Here we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human protein interactions. We show that experiments can orthogonally confirm higher-confidence models. We identify 3,137 high-confidence models, of which 1,371 have no homology to a known structure. We identify interface residues harboring disease mutations, suggesting potential mechanisms for pathogenic variants. Groups of interface phosphorylation sites show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple protein interactions as signaling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies helping to expand our understanding of human cell biology. Here the authors explore the ability of AlphaFold2 to predict structures across the human protein-protein interactome and the limitations thereof.
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影响因子：
16.6
作者：
Bryant P;Pozzati G;Elofsson A
通讯作者：
Elofsson A
影响因子：
16.6
作者：
Green AG;Elhabashy H;Brock KP;Maddamsetti R;Kohlbacher O;Marks DS
通讯作者：
Marks DS
影响因子：
14.9
作者：
Eliseev B;Yeramala L;Leitner A;Karuppasamy M;Raimondeau E;Huard K;Alkalaeva E;Aebersold R;Schaffitzel C
通讯作者：
Schaffitzel C
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：
14.8
作者：
Klykov, Oleg;Steigenberger, Barbara;Scheltema, Richard A.
通讯作者：
Scheltema, Richard A.