Bergdoll M, Eltis L D, Cameron A D, Dumas P, Bolin J T
Laboratoire de Biologie Structurale, Institut de Génétique et de Biologie Moléculaire et Cellulaire du CNRS, Illkirch, France.
Protein Sci. 1998 Aug;7(8):1661-70. doi: 10.1002/pro.5560070801.
The crystal structures of three proteins of diverse function and low sequence similarity were analyzed to evaluate structural and evolutionary relationships. The proteins include a bacterial bleomycin resistance protein, a bacterial extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as phylogenetic analyses, strongly indicate that the modern family of proteins represented by these structures arose through a rich evolutionary history that includes multiple gene duplication and fusion events. These events appear to be historically shared in some cases, but parallel and historically independent in others. A significant early event is proposed to be the establishment of metal-binding in an oligomeric ancestor prior to the first gene fusion. Variations in the spatial arrangements of homologous modules are observed that are consistent with the structural principles of three-dimensional domain swapping, but in the unusual context of the formation of larger monomers from smaller dimers or tetramers. The comparisons support a general mechanism for metalloprotein evolution that exploits the symmetry of a homooligomeric protein to originate a metal binding site and relies upon the relaxation of symmetry, as enabled by gene duplication, to establish and refine specific functions.
分析了三种功能各异且序列相似性较低的蛋白质的晶体结构，以评估其结构和进化关系。这些蛋白质包括一种细菌博来霉素抗性蛋白、一种细菌双加氧酶和人类乙二醛酶I。结构比较以及系统发育分析强烈表明，以这些结构为代表的现代蛋白质家族起源于丰富的进化历史，其中包括多个基因复制和融合事件。这些事件在某些情况下似乎是历史上共有的，但在其他情况下是平行且历史上独立的。一个重要的早期事件被认为是在第一次基因融合之前，在一个寡聚体祖先中建立金属结合。观察到同源模块空间排列的变化，这与三维结构域交换的结构原理一致，但处于由较小的二聚体或四聚体形成较大单体的不寻常背景下。这些比较支持了金属蛋白进化的一般机制，该机制利用同寡聚体蛋白的对称性来产生金属结合位点，并依赖于基因复制所促成的对称性松弛来建立和完善特定功能。
