AlphaFold-Predicted Structures of KCTD Proteins Unravel Previously Undetected Relationships among the Members of the Family.
AlphaFold-Predicted Structures of KCTD Proteins Unravel Previously Undetected Relationships among the Members of the Family.
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DOI：
10.3390/biom11121862
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发表时间：
2021-12-10
期刊：
影响因子：
5.5
通讯作者：
Vitagliano L
中科院分区：
文献类型：
--
作者：
Esposito L;Balasco N;Smaldone G;Berisio R;Ruggiero A;Vitagliano L
KCTD蛋白最显著的特征之一是它们参与明显不相关但基本的生理病理过程。不幸的是，这个蛋白质家族的全面的结构-功能关系受到了缺乏结构数据的阻碍。由于AlphaFold（AF）预测的蛋白质三维模型的发布，这种情况正在迅速改变。在这里，我们利用AF数据库中包含的结构信息来深入了解KCTD家族成员之间的关系，目的是促进这些蛋白质在许多生物过程中发挥关键作用的结构和分子基础的定义。从这项研究中出现的最重要的发现是，除了BTB结构域之外，这些蛋白质中的绝大多数还在C-末端区域中共享结构相似的结构域，尽管在该区域中没有可检测到的一般序列相似性。使用这个域作为参考，我们生成了一个新的和全面的基于结构的伪系统发育树，解开以前未检测到的蛋白质家族之间的相似性。特别是，我们生成了一个新的KCTD蛋白质聚类，这将为解释其许多功能提供坚实的基础。
One of the most striking features of KCTD proteins is their involvement in apparently unrelated yet fundamental physio-pathological processes. Unfortunately, comprehensive structure–function relationships for this protein family have been hampered by the scarcity of the structural data available. This scenario is rapidly changing due to the release of the protein three-dimensional models predicted by AlphaFold (AF). Here, we exploited the structural information contained in the AF database to gain insights into the relationships among the members of the KCTD family with the aim of facilitating the definition of the structural and molecular basis of key roles that these proteins play in many biological processes. The most important finding that emerged from this investigation is the discovery that, in addition to the BTB domain, the vast majority of these proteins also share a structurally similar domain in the C-terminal region despite the absence of general sequence similarities detectable in this region. Using this domain as reference, we generated a novel and comprehensive structure-based pseudo-phylogenetic tree that unraveled previously undetected similarities among the protein family. In particular, we generated a new clustering of the KCTD proteins that will represent a solid ground for interpreting their many functions.
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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
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作者：
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Bamshad, Michael J.
DOI：
10.1016/j.bbalip.2019.08.010
发表时间：
2019-12-01
影响因子：
4.8
作者：
Pirone, Luciano;Smaldone, Giovanni;Pedone, Emilia
通讯作者：
Pedone, Emilia
影响因子：
3.5
作者：
Smaldone, Giovanni;Pirone, Luciano;Ciccarelli, Luciano
通讯作者：
Ciccarelli, Luciano