Lolkema Juke S, Dobrowolski Adam, Slotboom Dirk-Jan
Molecular Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands.
J Mol Biol. 2008 May 2;378(3):596-606. doi: 10.1016/j.jmb.2008.03.005. Epub 2008 Mar 12.
X-ray crystallography has revealed that many integral membrane proteins consist of two domains with a similar fold but opposite (antiparallel) orientation in the membrane. The proteins are believed to have evolved by gene duplication and gene fusion events from a dual topology ancestral membrane protein, that adapted both orientations in the membrane and formed antiparallel homodimers. Here, we present a detailed analysis of the DUF606 family of bacterial membrane proteins that contains the entire collection of intermediate states of such an evolutionary pathway: single genes that would code for dual topology homodimeric proteins, paired genes coding for homologous proteins with a fixed but opposite orientation in the membrane that would form heterodimers, and fused genes that encode antiparallel two-domain fusion proteins. Two types of paired genes can be discriminated corresponding to the order in which the genes coding for the two oppositely oriented proteins occur in the operon. On the protein level, the heterodimers resulting from the two types of gene pairs are indistinguishable. In contrast, two types of fused genes corresponding to the two possible orders in which the oppositely oriented domains are present in the encoded proteins, do result in discernible types of proteins. The large number of genetic and protein states in the DUF606 family allowed for a detailed phylogenic analysis that revealed a total of nine independent duplication events in the DUF606 family, five of which resulted in paired genes, and four resulted in fused genes. Noticeably, there was no evidence for a sequential mechanism in which fusions evolve from a pair of genes. Rather, an evolutionary mechanism is proposed by which antiparallel two-domain proteins are the direct result of a gene duplication event. Combining the phylogeny of proteins and hosting microorganisms allowed for a reconstruction of the evolutionary pathway.
X射线晶体学研究表明，许多整合膜蛋白由两个结构域组成，这两个结构域具有相似的折叠方式，但在膜中的方向相反（反平行）。据信，这些蛋白质是通过基因复制和基因融合事件从一种双拓扑结构的祖先膜蛋白进化而来的，这种祖先膜蛋白能够适应膜中的两种方向，并形成反平行同二聚体。在此，我们对细菌膜蛋白的DUF606家族进行了详细分析，该家族包含了这种进化途径的所有中间状态：编码双拓扑同二聚体蛋白的单个基因、编码在膜中具有固定但相反方向的同源蛋白（可形成异二聚体）的配对基因，以及编码反平行双结构域融合蛋白的融合基因。根据编码两种方向相反蛋白质的基因在操纵子中出现的顺序，可以区分出两种类型的配对基因。在蛋白质水平上，由这两种类型的基因对产生的异二聚体无法区分。相比之下，对应于编码蛋白质中相反方向结构域的两种可能顺序的两种类型的融合基因，确实会产生可区分的蛋白质类型。DUF606家族中大量的基因和蛋白质状态使得进行详细的系统发育分析成为可能，该分析揭示了DUF606家族中总共九个独立的复制事件，其中五个导致了配对基因的产生，四个导致了融合基因的产生。值得注意的是，没有证据表明融合是从一对基因逐步进化而来的机制。相反，我们提出了一种进化机制，即反平行双结构域蛋白是基因复制事件的直接结果。结合蛋白质和宿主微生物的系统发育，能够重建进化途径。
Zotero 插件