Exons and the structure, function and evolution of haemoglobin
Exons and the structure, function and evolution of haemoglobin
复制标题
外显子与血红蛋白的结构、功能和进化
作者：
C. Blake
在过去的几周里，《自然》杂志上出现了一系列直接与血红蛋白基因编码序列或外显子的意义有关的论文。在小鼠α-和/或J-球蛋白基因中，存在三个外显子，分别对应于氨基酸残基1-31、32-99和100-141;以及1-30、31-104和105-146。当α-和β-球蛋白的氨基酸序列被比对以使它们的结构同源性最大化时，它们的内含子/外显子连接点重合。这立即表明外显子的“意义”在某种程度上与蛋白质的结构和功能有关。最近的论文通过分析外显子编码区的结构，功能和血红蛋白分子的进化来解决这个问题。Go 1巧妙地使用了对角线图（见图）来定义多肽链上距离较远的区域（> 27。A）在珠蛋白折叠中彼此分离。他发现有四个这样的区域，它们不是域，但可以被称为子域，或者“紧凑结构”。当包括在对角线图上时，外显子边界将这些紧凑结构彼此整齐地分开，除了由两个紧凑结构组成的大的中央外显子区域。因此，Go提出，中央外显子区可能由两个“融合”外显子区组成，在残基66和71之间的某个地方分裂。值得注意的是，这一预测很快就被马克尔及其同事2（见本期《自然》，第677页）在测定大豆豆血红蛋白基因的结构时所证实。该基因由4个外显子组成，分别对应于氨基酸残基1-32、32-68、69-103、104-C末端。马克尔的结果表明，外显子通常是非常稳定的，但它们可以经历。融合或分离。Go语言基于蛋白质结构成功地预测了外显子，这为外显子对应于紧密的蛋白质结构的观点提供了有力的支持。由于吉尔伯特关于外显子与蛋白质功能单位之间关系的论述似乎已在溶菌酶中得到验证，因此对血红蛋白这方面的考虑特别令人感兴趣。在血红蛋白中，功能相关性始于假设6，即中央外显子区域似乎对应于血红蛋白结合单位。这一建议
OVER the last few weeks there has been a flurry of papers in Nature that bear directly on the meaning of coding sequences or exons in the haemoglobin genes. In the mouse a-and/J-glob in genes there are three exons corresponding to amino acid residues 1-31, 32-99 and 100-141; and 1-30, 31-104 and 105-146, respectively. When the amino acid sequences of the a-and (3-globins are aligned to maximize their structural homologies, their intron/exon junctions coincide. This immediately suggests that the'meaning'of the exons is related in some way to the structure and function of the protein. The recent papers address themselves to the problem by analysing the exon-encoded regions in terms of the structure, function and evolution of the haemoglobin molecule. Go1 has ingeniously used the diagonal plot (see the figure) to define regions of the polypeptide chain that are distant (> 27. A) from one another in the globin fold. He has found that there are four such regions, which are not domains, but which can be called sub-domains, or perhaps' compact structures'. When included on the diagonal plot the exon boundaries neatly divide off these compact structures from one another, with the exception of the large central exonic region which is composed of two compact structures. Because of this Go suggested that the central exonic region might consist of two'fused'exonic regions with a division somewhere between residues 66 and 71. Quite remarkably this prediction has been rapidly verified by Marcker and colleagues2 (see this issue of Nature, p. 677) in their determination of the structure of the leghaemoglobin gene from soybean. This gene is composed of four exons, corresponding to amino acid residues 1-32, 32-68, 69-103, 104-C terminus. Marcker's results suggest that exons are generally very stable, but that they can undergo. fusion or separation. Go's successful prediction of an exon on the basis of protein structure adds powerful additional support to the idea3 that they correspond to compact protein structures.As Gilbert's suggestion4 of a relation between exons and protein functional units appears to have been validated in lysozyme5, consideration of this aspect of haemoglobin is of particular interest. In haemoglobin the functional correlation began with the suggestion6 that the central exonic region appeared to correspond to a haem-binding unit. This suggestion was