Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality.
Evolutionary origin of a secondary structure: π-helices as cryptic but widespread insertional variations of α-helices that enhance protein functionality.
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DOI：
10.1016/j.jmb.2010.09.034
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发表时间：
2010-11-26
影响因子：
5.6
通讯作者：
Karplus PA
中科院分区：
文献类型：
--
作者：
Cooley RB;Arp DJ;Karplus PA
正式带注释的π-螺旋在蛋白质结构中很少见，但与功能位点相关。通过对蛋白质结构的分析，我们发现π-螺旋结构与α-凸起、α-动脉瘤、π-凸起和环出结构相同，并且是由单个残基插入α-螺旋而进化而来的。这个新发现的进化起源解释了为什么π螺旋是神秘的，尽管存在于15%的已知蛋白质中却很少被注释，以及为什么它们倾向于与功能相关。对不同类铁蛋白超家族中π-螺旋的分析表明，π-螺旋在蛋白质家族中具有保守的倾向，并确定了一个假定的含π-螺旋的原始前体，一个核糖核苷酸还原酶家族的“缺失链”中间形式，残留π-螺旋，以及一个被我们称为蠕动样移位的π-螺旋的新功能。这种对π-螺旋的新理解为这个通常被忽视的基序成为一个值得注意的特征铺平了道路，这将有助于追踪许多蛋白质家族的进化，指导蛋白质和π-螺旋功能的研究，并为蛋白质工程工具箱提供额外的工具。
Formally annotated π-helices are rare in protein structure but have been correlated with functional sites. Here, we analyze protein structures to show that π-helices are the same as structures known as α-bulges, α-aneurisms, π-bulges, and looping-outs and are evolutionarily derived by the insertion of a single residue into an α-helix. This newly discovered evolutionary origin explains both why π-helices are cryptic, being rarely annotated despite occurring in 15% of known proteins, and why they tend to be associated with function. An analysis of the π-helices in the diverse ferritin-like superfamily illustrates their tendency to be conserved in protein families, and identifies a putative π-helix-containing primordial precursor, a “missing link” intermediary form of the ribonucleotide reductase family, vestigial π-helices, and a novel function for π-helices we term peristaltic-like shifts. This new understanding of π-helices paves the way for this generally overlooked motif to become a noteworthy feature that will aid tracing the evolution of many protein families, guide investigations of protein and π-helix functionality, and contribute additional tools to the protein engineering toolkit.
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DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
影响因子：
56.9
作者：
Högbom, M;Stenmark, P;Nordlund, P
通讯作者：
Nordlund, P
影响因子：
2.8
作者：
Cooley, Richard B.;Dubbel, Bradley L.;Arp, Daniel J.
通讯作者：
Arp, Daniel J.
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
DOI：
10.1073/pnas.0901522106
发表时间：
2009-06-16
影响因子：
11.1
作者：
Bloom, Jesse D.;Arnold, Frances H.
通讯作者：
Arnold, Frances H.