Assembly reflects evolution of protein complexes.
Assembly reflects evolution of protein complexes.
复制标题
DOI：
10.1038/nature06942
复制
发表时间：
2008-06-26
期刊：
影响因子：
64.8
通讯作者：
Teichmann, Sarah A.
中科院分区：
文献类型：
--
作者：
Levy, Emmanuel D.;Erba, Elisabetta Boeri;Robinson, Carol V.;Teichmann, Sarah A.
异构体是由蛋白质单位的自我相互作用的拷贝形成的。这在功能上很重要，就像在变构中一样，在结构上也是至关重要的，因为同质异构体的错误组装与疾病有关。同聚体广泛存在，50%-70%的已知四元状态的蛋白质组装成这样的结构。尽管它们的普遍存在，它们在细胞机械进化中的作用，以及它们在设计新的分子机器方面的潜力，人们对在细胞进化和组装水平上驱动同质异构体形成的机制知之甚少。在这里，我们提供了超过5,000个独特的原子结构的分析，并表明同质异构体的四级结构在超过70%的蛋白质对中是保守的，这些蛋白质对的序列一致性只有30%。在蛋白质家族的成员中，四级结构不是保守的，详细的研究揭示了蛋白质在不同的四级结构类型之间传递的明确的进化路径。此外，我们通过扰动复合体内的亚基界面和质谱分析表明，(Dis)组装途径模拟了进化途径。这些数据代表了与海克尔的胚胎发育进化范式的分子类比，在该范式中，复合体组装中的中间体代表着一种出现在其自身进化史上的形式。我们的自组装模型仅根据其晶体结构就可以可靠地预测络合物的演化和组装。
A homomer is formed by self-interacting copies of a protein unit. This is functionally important, as in allostery, and structurally crucial because mis-assembly of homomers is implicated in disease. Homomers are widespread, with 50–70% of proteins with a known quaternary state assembling into such structures. Despite their prevalence, their role in the evolution of cellular machinery and the potential for their use in the design of new molecular machines, little is known about the mechanisms that drive formation of homomers at the level of evolution and assembly in the cell. Here we present an analysis of over 5,000 unique atomic structures and show that the quaternary structure of homomers is conserved in over 70% of protein pairs sharing as little as 30% sequence identity. Where quaternary structure is not conserved among the members of a protein family, a detailed investigation revealed well-defined evolutionary pathways by which proteins transit between different quaternary structure types. Furthermore, we show by perturbing subunit interfaces within complexes and by mass spectrometry analysis, that the (dis)assembly pathway mimics the evolutionary pathway. These data represent a molecular analogy to Haeckel's evolutionary paradigm of embryonic development, where an intermediate in the assembly of a complex represents a form that appeared in its own evolutionary history. Our model of self-assembly allows reliable prediction of evolution and assembly of a complex solely from its crystal structure.
登录
查看更多内容
影响因子：
3.4
作者：
Powers, ET;Powers, DL
通讯作者：
Powers, DL
影响因子：
4.3
作者：
Levy ED;Pereira-Leal JB;Chothia C;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
64.8
作者：
Iber, D;Clarkson, J;Campbell, ID
通讯作者：
Campbell, ID
影响因子：
14.8
作者：
Hernandez, Helena;Robinson, Carol V.
通讯作者：
Robinson, Carol V.
影响因子：
5.7
作者：
Levy, Emmanuel D.
通讯作者：
Levy, Emmanuel D.