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核心真核蛋白复合物的计算结构。

Computed structures of core eukaryotic protein complexes.

机构信息

Department of Biochemistry, University of Washington, Seattle, WA, USA.

Institute for Protein Design, University of Washington, Seattle, WA, USA.

出版信息

Science. 2021 Dec 10;374(6573):eabm4805. doi: 10.1126/science.abm4805.


DOI:10.1126/science.abm4805
PMID:34762488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7612107/
Abstract

Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there are likely many interactions not yet identified. We take advantage of advances in proteome-wide amino acid coevolution analysis and deep-learning–based structure modeling to systematically identify and build accurate models of core eukaryotic protein complexes within the proteome. We use a combination of RoseTTAFold and AlphaFold to screen through paired multiple sequence alignments for 8.3 million pairs of yeast proteins, identify 1505 likely to interact, and build structure models for 106 previously unidentified assemblies and 806 that have not been structurally characterized. These complexes, which have as many as five subunits, play roles in almost all key processes in eukaryotic cells and provide broad insights into biological function.

摘要

蛋白质-蛋白质相互作用在生物学中起着至关重要的作用,但许多真核生物蛋白质复合物的结构尚不清楚,可能还有许多尚未被发现的相互作用。我们利用在全蛋白质组范围内氨基酸共进化分析和基于深度学习的结构建模方面的进展,系统地识别和构建蛋白质组内核心真核生物蛋白质复合物的精确模型。我们结合使用了 RoseTTAFold 和 AlphaFold,通过对 830 万对酵母蛋白的成对多重序列比对进行筛选,鉴定出 1505 对可能相互作用的蛋白质,并为 106 个先前未被识别的组装体和 806 个尚未进行结构特征分析的组装体构建了结构模型。这些复合物有多达五个亚基,参与真核细胞中几乎所有关键过程,并为深入了解生物学功能提供了广泛的见解。

相似文献

[1]
Computed structures of core eukaryotic protein complexes.

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[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Molecular basis for substrate recruitment to the PRMT5 methylosome.

Mol Cell. 2021-9-2

[2]
SMC complexes are guarded by the SUMO protease Ulp2 against SUMO-chain-mediated turnover.

Cell Rep. 2021-8-3

[3]
Accurate prediction of protein structures and interactions using a three-track neural network.

Science. 2021-8-20

[4]
Translational control of stem cell function.

Nat Rev Mol Cell Biol. 2021-10

[5]
Highly accurate protein structure prediction with AlphaFold.

Nature. 2021-8

[6]
Cryo-EM structure of TFIIH/Rad4-Rad23-Rad33 in damaged DNA opening in nucleotide excision repair.

Nat Commun. 2021-6-7

[7]
DOE JGI Metagenome Workflow.

mSystems. 2021-5-18

[8]
Smc5/6 functions with Sgs1-Top3-Rmi1 to complete chromosome replication at natural pause sites.

Nat Commun. 2021-4-8

[9]
Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function.

Nucleic Acids Res. 2021-4-6

[10]
Large-scale discovery of protein interactions at residue resolution using co-evolution calculated from genomic sequences.

Nat Commun. 2021-3-2

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