The combined effects of amino acid substitutions and indels on the evolution of structure within protein families.
The combined effects of amino acid substitutions and indels on the evolution of structure within protein families.
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DOI：
10.1371/journal.pone.0014316
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发表时间：
2010-12-13
期刊：
影响因子：
3.7
通讯作者：
Gao P
中科院分区：
文献类型：
--
作者：
Zhang Z;Wang Y;Wang L;Gao P
在蛋白质进化过程中，蛋白质家族内的序列变异会引起蛋白质结构和功能的变化。然而，结构往往比序列和功能更保守。这就引出了一个有趣的问题：序列变异产生结构变化的进化机制是什么？为了研究这个问题，我们专注于最常见的序列变异类型：氨基酸取代和插入/缺失（indels）。在这里，他们的蛋白质家族内的蛋白质结构进化的综合影响进行了研究。对75个含有20个或更多非冗余结构的同源结构家族（来自SCOP）的序列-结构相关性分析表明，在这些家族中的大多数家族中，在统计上，取代和插入缺失的量与结构变异的程度之间存在双线性相关性。进行序列非同一性百分比（PNI）和标准化缺口数（SNG）与RMSD的双线性回归。来自回归分析的系数可用于估计由每个取代单元（结构取代敏感性，SSS）和由每个indel单元（结构indel敏感性，SIDS）引起的结构变化。对52个双线性拟合复相关系数高、回归系数有统计学意义的家系分析表明，SSS主要受二硫键制约，对SIDS几乎没有影响。结合氨基酸取代和插入缺失的双线性模型可以合理地解释同源蛋白质家族的结构变化。这些结果可能进一步提高我们对蛋白质结构进化机制的理解。
In the process of protein evolution, sequence variations within protein families can cause changes in protein structures and functions. However, structures tend to be more conserved than sequences and functions. This leads to an intriguing question: what is the evolutionary mechanism by which sequence variations produce structural changes? To investigate this question, we focused on the most common types of sequence variations: amino acid substitutions and insertions/deletions (indels). Here their combined effects on protein structure evolution within protein families are studied. Sequence-structure correlation analysis on 75 homologous structure families (from SCOP) that contain 20 or more non-redundant structures shows that in most of these families there is, statistically, a bilinear correlation between the amount of substitutions and indels versus the degree of structure variations. Bilinear regression of percent sequence non-identity (PNI) and standardized number of gaps (SNG) versus RMSD was performed. The coefficients from the regression analysis could be used to estimate the structure changes caused by each unit of substitution (structural substitution sensitivity, SSS) and by each unit of indel (structural indel sensitivity, SIDS). An analysis on 52 families with high bilinear fitting multiple correlation coefficients and statistically significant regression coefficients showed that SSS is mainly constrained by disulfide bonds, which almost have no effects on SIDS. Structural changes in homologous protein families could be rationally explained by a bilinear model combining amino acid substitutions and indels. These results may further improve our understanding of the evolutionary mechanisms of protein structures.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
2.1
作者：
Notredame, C
通讯作者：
Notredame, C
影响因子：
5.6
作者：
PASCARELLA, S;ARGOS, P
通讯作者：
ARGOS, P
影响因子：
3
作者：
Martinez, Leandro;Andreani, Roberto;Martinez, Jose Mario
通讯作者：
Martinez, Jose Mario
影响因子：
8
作者：
FLORES, TP;ORENGO, CA;THORNTON, JM
通讯作者：
THORNTON, JM