美国芝加哥大学Joseph W. Thornton研究组取得最新进展。他们揭示了血红蛋白进化复杂性的起源。2020年5月20日，《自然》发表了这一成果。
他们使用祖先蛋白重建和生物物理分析方法来阐明脊椎动物血红蛋白的起源，脊椎动物血红蛋白是旁系α-和β-亚基的异四聚体，它通过以适度亲和力协同结合氧来介导呼吸氧的运输和交换。他们证明了现代血红蛋白是从古老的单体演变而来的，并表征了现代四聚体通过其进化的历史“缺失环节”——一种具有高氧亲和力的非协同同型二聚体，在基因复制之前就已经存在，产生了不同的α-和β-亚基。
仅将两个复制后的历史替代物重新引入到祖先蛋白中，就足以通过与相对的亚基上更古老的残基形成有利的接触而引起明显的四聚化。这些表面代替显著降低了氧亲和力，甚至赋予了协同作用，因为氧结合位点与多聚界面之间的古老联系已经是蛋白质结构的固有特征。
他们的发现表明，进化可以通过简单的遗传机制产生新的复杂分子结构和功能，这些机制将现有的生物物理结构募集到更高级别的架构中。
据了解，大多数蛋白质结合成具有特定结构的多聚体复合物，这些结构通常具有功能特性，例如协同配体结合或变构调节。目前尚无关于多聚体及其功能在进化过程中如何产生的详细见解。
附：英文原文
Title: Origin of complexity in haemoglobin evolution
Author: Arvind S. Pillai, Shane A. Chandler, Yang Liu, Anthony V. Signore, Carlos R. Cortez-Romero, Justin L. P. Benesch, Arthur Laganowsky, Jay F. Storz, Georg K. A. Hochberg, Joseph W. Thornton
Issue&Volume: 2020-05-20
Abstract: Most proteins associate into multimeric complexes with specific architectures1,2, which often have functional properties such as cooperative ligand binding or allosteric regulation3. No detailed knowledge is available about how any multimer and its functions arose during evolution. Here we use ancestral protein reconstruction and biophysical assays to elucidate the origins of vertebrate haemoglobin, a heterotetramer of paralogous α- and β-subunits that mediates respiratory oxygen transport and exchange by cooperatively binding oxygen with moderate affinity. We show that modern haemoglobin evolved from an ancient monomer and characterize the historical ‘missing link’ through which the modern tetramer evolved—a noncooperative homodimer with high oxygen affinity that existed before the gene duplication that generated distinct α- and β-subunits. Reintroducing just two post-duplication historical substitutions into the ancestral protein is sufficient to cause strong tetramerization by creating favourable contacts with more ancient residues on the opposing subunit. These surface substitutions markedly reduce oxygen affinity and even confer cooperativity, because an ancient linkage between the oxygen binding site and the multimerization interface was already an intrinsic feature of the protein’s structure. Our findings establish that evolution can produce new complex molecular structures and functions via simple genetic mechanisms that recruit existing biophysical features into higher-level architectures.
DOI: 10.1038/s41586-020-2292-y
Source: https://www.nature.com/articles/s41586-020-2292-y
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
