Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family.
Alphafold Predictions Provide Insights into the Structural Features of the Functional Oligomers of All Members of the KCTD Family.
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DOI：
10.3390/ijms232113346
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发表时间：
2022-11-01
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
寡聚化赋予蛋白质一些关键性质，如额外的稳定性，远程变构调节，以及单体对应物无法获得的伙伴关系。在进化过程中，寡聚化是如何实现和保持的，这是一个具有显著科学意义的课题。通过利用AlphaFold（AF）中实现的机器学习算法在预测蛋白质结构方面的能力，本文中，我们报告了对KCTD蛋白质家族所有成员的功能性寡聚体的结构状态的全面分析。有趣的是，我们的方法导致了KCNRG，KCTD 6，KCTD 4，KCTD 7，KCTD 9和KCTD 14的五聚体状态的可靠的三维模型的识别，并可能为KCTD 11和KCTD 21参与关键的生物过程，以前未从结构的角度来表征。尽管对于大多数这些蛋白质，CTD结构域缺乏任何序列相似性，但它们共享一些重要的结构特征，例如螺旋桨样结构，其具有由五个暴露的和规则的β链界定的中心空腔。此外，相关蛋白质KCTD 7和KCTD 14的结构，虽然是五聚体，但似乎以CTD区域的不同组织为特征，五条链形成具有大空腔的环状结构。我们的预测还表明，该家族的其他成员，如KCTD 10，KCTD 13和TNFAIP 1，呈现出强烈的二聚体状态的倾向。尽管本文报道的功能性寡聚体的结构代表了需要额外验证的模型，但它们提供了KCTD蛋白寡聚化的一致和全局观点。
Oligomerization endows proteins with some key properties such as extra-stabilization, long-range allosteric regulation(s), and partnerships not accessible to their monomeric counterparts. How oligomerization is achieved and preserved during evolution is a subject of remarkable scientific relevance. By exploiting the abilities of the machine-learning algorithms implemented in AlphaFold (AF) in predicting protein structures, herein, we report a comprehensive analysis of the structural states of functional oligomers of all members of the KCTD protein family. Interestingly, our approach led to the identification of reliable three-dimensional models for the pentameric states of KCNRG, KCTD6, KCTD4, KCTD7, KCTD9, and KCTD14 and possibly for KCTD11 and KCTD21 that are involved in key biological processes and that were previously uncharacterized from a structural point of view. Although for most of these proteins, the CTD domains lack any sequence similarity, they share some important structural features, such as a propeller-like structure with a central cavity delimited by five exposed and regular β-strands. Moreover, the structure of the related proteins KCTD7 and KCTD14, although pentameric, appears to be characterized by a different organization of the CTD region, with the five chains forming a circle-like structure with a large cavity. Our predictions also suggest that other members of the family, such as KCTD10, KCTD13, and TNFAIP1, present a strong propensity to assume dimeric states. Although the structures of the functional oligomers reported herein represent models that require additional validations, they provide a consistent and global view of KCTD protein oligomerization.
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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：
5.7
作者：
Ingles-Prieto, Alvaro;Ibarra-Molero, Beatriz;Delgado-Delgado, Asuncion;Perez-Jimenez, Raul;Fernandez, Julio M.;Gaucher, Eric A.;Sanchez-Ruiz, Jose M.;Gavira, Jose A.
通讯作者：
Gavira, Jose A.
影响因子：
9.8
作者：
Marneros, Alexander G.;Beck, Anita E.;Bamshad, Michael J.
通讯作者：
Bamshad, Michael J.
影响因子：
5.5
作者：
Esposito L;Balasco N;Smaldone G;Berisio R;Ruggiero A;Vitagliano L
通讯作者：
Vitagliano L
DOI：
10.1016/j.bbapap.2014.04.006
发表时间：
2014-07-01
影响因子：
3.2
作者：
Balasco, Nicole;Pirone, Luciano;Vitagliano, Luigi
通讯作者：
Vitagliano, Luigi