MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Sci Adv. 2017 Sep 1;3(9):e1602937. doi: 10.1126/sciadv.1602937. eCollection 2017 Sep.
Homeodomain proteins control the developmental transition between the haploid and diploid phases in several eukaryotic lineages, but it is not known whether this regulatory mechanism reflects the ancestral condition or, instead, convergent evolution. We have characterized the mating-type locus of the amoebozoan , which encodes two pairs of small proteins that determine the three mating types of this species; none of these proteins display recognizable homology to known families. We report that the nuclear magnetic resonance structures of two of them, MatA and MatB, contain helix-turn-helix folds flanked by largely disordered amino- and carboxyl-terminal tails. This fold closely resembles that of homeodomain transcription factors, and, like those proteins, MatA and MatB each bind DNA characteristically using the third helix of their folded domains. By constructing chimeric versions containing parts of MatA and MatB, we demonstrate that the carboxyl-terminal tail, not the central DNA binding motif, confers mating specificity, providing mechanistic insight into how a third mating type might have originated. Finally, we show that these homeodomain-like proteins specify zygote function: Hemizygous diploids, formed in crosses between a wild-type strain and a null mutant, grow and differentiate identically to haploids. We propose that MatA and MatB are divergent homeodomain proteins with a conserved function in triggering the haploid-to-diploid transition that can be traced back to the last common ancestor of eukaryotes.
同源结构域蛋白控制着几种真核生物谱系中从单倍体到二倍体阶段的发育转变，但尚不清楚这种调控机制是反映了祖先的状况，还是趋同进化的结果。我们已经对变形虫的交配型基因座进行了特征描述，该基因座编码两对决定该物种三种交配型的小蛋白；这些蛋白中没有一个与已知家族具有可识别的同源性。我们报告称，其中两种蛋白，MatA 和 MatB 的核磁共振结构包含由大部分无序的氨基和羧基末端尾巴环绕的螺旋-转角-螺旋折叠。这种折叠结构与同源结构域转录因子非常相似，并且与这些蛋白一样，MatA 和 MatB 都使用其折叠结构域的第三个螺旋特征性地结合 DNA。通过构建包含 MatA 和 MatB 部分的嵌合版本，我们证明羧基末端尾巴而不是中央 DNA 结合基序赋予了交配特异性，为第三交配型可能起源的机制提供了深入的了解。最后，我们表明这些同源结构域样蛋白决定了受精卵的功能：在野生型菌株和一个 缺失突变体之间的杂交中形成的半合子二倍体，其生长和分化与单倍体完全相同。我们提出，MatA 和 MatB 是具有保守功能的趋同进化的同源结构域蛋白，可追溯到真核生物的最后共同祖先，触发了从单倍体到二倍体的转变。
