Integrative structure determination of histones H3 and H4 using genetic interactions.
Integrative structure determination of histones H3 and H4 using genetic interactions.
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DOI：
10.1111/febs.16435
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发表时间：
2023-05
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影响因子：
--
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集成结构建模越来越多地用于确定生物装配的结构，特别是那些结构异构的结构。最近，我们报道了如何将体内遗传相互作用测量转化为结构建模的空间约束：首先，为每个点突变和数千个基因缺失或环境扰动生成表型谱。随后，表型谱相似性转化为突变残基对的距离限制。我们通过确定组蛋白H3-H4复合物的结构来说明这种方法。该方法在我们的开源IMP程序中实现，通过允许基于体内数据的结构表征而无需纯化目标系统，扩展了结构生物学工具箱。我们将遗传相互作用测量与其他结构信息来源进行了比较，例如残基共同进化和复杂亚基的深度学习结构预测。我们还建议确定遗传相互作用可能受益于新技术，例如CRISPR-Cas9基因编辑方法，特别是针对哺乳动物细胞。最后，我们强调了利用遗传相互作用来确定顽固性生物分子结构的机会，例如无序蛋白质，瞬时蛋白质组装和宿主-病原体蛋白质复合物。
Integrative structure modeling is increasingly used for determining the architectures of biological assemblies, especially those that are structurally heterogeneous. Recently, we reported on how to convert in vivo genetic interaction measurements into spatial restraints for structural modeling: first, phenotypic profiles are generated for each point mutation and thousands of gene deletions or environmental perturbations. Following, the phenotypic profile similarities are converted into distance restraints on the pairs of mutated residues. We illustrate the approach by determining the structure of the histone H3-H4 complex. The method is implemented in our open-source IMP program, expanding the structural biology toolbox by allowing structural characterization based on in vivo data without the need to purify the target system. We compare genetic interaction measurements to other sources of structural information, such as residue coevolution and deep-learning structure prediction of complex subunits. We also suggest that determining genetic interactions could benefit from new technologies, such as CRISPR-Cas9 approaches to gene editing, especially for mammalian cells. Finally, we highlight the opportunity for using genetic interactions to determine recalcitrant biomolecular structures, such as those of disordered proteins, transient protein assemblies, and host-pathogen protein complexes.
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影响因子：
2.7
作者：
Crehuet R;Buigues PJ;Salvatella X;Lindorff-Larsen K
通讯作者：
Lindorff-Larsen K
DOI：
10.1038/s41576-021-00441-w
发表时间：
2022-06
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Braberg H;Echeverria I;Kaake RM;Sali A;Krogan NJ
通讯作者：
Krogan NJ
影响因子：
5.8
作者：
Albanese, Davide;Filosi, Michele;Furlanello, Cesare
通讯作者：
Furlanello, Cesare
影响因子：
7
作者：
Hagen, Nicole;Bayer, Karen;Schindler, Michael
通讯作者：
Schindler, Michael
DOI：
10.1073/pnas.1915542117
发表时间：
2020-02-25
影响因子：
11.1
作者：
Gutierrez, Craig;Chemmama, Ilan E.;Huang, Lan
通讯作者：
Huang, Lan