Why similar protein sequences encode similar three-dimensional structures?
Why similar protein sequences encode similar three-dimensional structures?
复制标题
DOI：
10.1007/s00214-009-0656-3
复制
发表时间：
2010-03-01
影响因子：
1.7
通讯作者：
Zielenkiewicz, Piotr
中科院分区：
文献类型：
--
作者：
Kaczanowski, Szymon;Zielenkiewicz, Piotr
进化上相关的蛋白质具有相似的序列。这种相似性被称为同源性，并且可以使用诸如Blosum 60的替换矩阵来描述。天然存在的同源蛋白质通常具有相似的稳定三级结构，这一事实被用于所谓的同源建模。相反，由Regan小组设计的人工蛋白质与链球菌IgG结合蛋白的B1结构域具有50%的相同序列，并且结构类似于蛋白质Rop。在这项研究中，我们提出了一个问题，即人工相似蛋白质序列（伪同源物）是否倾向于编码类似的蛋白质结构，例如自然界中存在的蛋白质。为了回答这个问题，我们根据Blosum 60替换矩阵作为已知的天然同源物，设计了与具有已知三维结构（模板结构）、相同数量的身份、相同组成和相同水平的同源性的序列同源的蛋白质序列（假同源物）集。我们比较了同系物和假同系物的结构特征，通过拟合它们的模板结构。这种结构的质量进行了评估，通过线程电位。使用三维同源模型测量包装质量。“假同系物”模型的包装质量比真实的同系物差。天然同源物在天然结构中比设计的序列具有更好的穿线潜力（指示更好的序列-结构拟合）。因此，我们已经表明，线程潜力和适当的包装是进化上更强烈的保守比序列同源性测量使用Blosum 60矩阵。我们的研究结果表明，三维蛋白质结构是进化上比预期的保守，由于序列保守。
Evolutionarily related proteins have similar sequences. Such similarity is called homology and can be described using substitution matrices such as Blosum 60. Naturally occurring homologous proteins usually have similar stable tertiary structures and this fact is used in so-called homology modeling. In contrast, the artificial protein designed by the Regan group has 50% identical sequence to the B1 domain of Streptococcal IgG-binding protein and a structure similar to the protein Rop. In this study, we asked the question whether artificial similar protein sequences (pseudohomologs) tend to encode similar protein structures, such as proteins existing in nature. To answer this question, we designed sets of protein sequences (pseudohomologs) homologous to sequences having known three-dimensional structures (template structures), same number of identities, same composition and equal level of homology, according to Blosum 60 substitution matrix as the known natural homolog. We compared the structural features of homologs and pseudohomologs by fitting them to the template structure. The quality of such structures was evaluated by threading potentials. The packing quality was measured using three-dimensional homology models. The packing quality of the models was worse for the "pseudohomologs" than for real homologs. The native homologs have better threading potentials (indicating better sequence-structure fit) in the native structure than the designed sequences. Therefore, we have shown that threading potentials and proper packing are evolutionarily more strongly conserved than sequence homology measured using the Blosum 60 matrix. Our results indicate that three-dimensional protein structure is evolutionarily more conserved than expected due to sequence conservation.