Takahashi N, Takahashi Y, Putnam F W
Department of Biology, Indiana University, Bloomington 47405.
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7403-7. doi: 10.1073/pnas.84.21.7403.
Proalbumins are rare genetic variants of human serum albumin containing a basic propeptide that is not removed during post-transcriptional processing because of a mutation in the site of excision, an Arg-Arg sequence. We have identified the amino acid substitutions in three different types of proalbumins designated Gainesville, Taipei, and Takefu. The first two proalbumins are identical to previously described proalbumins of the Christchurch and Lille types, respectively, and exhibit the characteristic properties of susceptibility to tryptic cleavage and of lower metal-binding affinity. Takefu is a third type of proalbumin and resists tryptic cleavage because of the substitution Arg-1----Pro. Each of the first two types of proalbumins has been identified in geographically separate, ethnically diverse populations and therefore must have arisen by independent mutations. There is some tendency for mutations in albumin to cluster in the propeptide sequence. Although the substitution His3----Gln in the genetic variant albumin Nagasaki-3 decreases metal-binding affinity, mutations further down the polypeptide chain have no such effect, nor is there any reduction of copper-binding affinity in albumin from patients with Wilson disease.
前清蛋白是人类血清白蛋白的罕见遗传变体，含有一种碱性前肽，由于切除位点（一个精氨酸 - 精氨酸序列）发生突变，该前肽在转录后加工过程中未被去除。我们已经确定了三种不同类型前清蛋白（分别命名为盖恩斯维尔、台北和武生）中的氨基酸替换。前两种前清蛋白分别与先前描述的克赖斯特彻奇型和里尔型前清蛋白相同，并表现出对胰蛋白酶裂解敏感和金属结合亲和力较低的特征性质。武生是第三种前清蛋白类型，由于精氨酸 - 1被替换为脯氨酸，它能抵抗胰蛋白酶裂解。前两种类型的前清蛋白已在地理上分离、种族多样的人群中被鉴定出来，因此必定是由独立突变产生的。白蛋白中的突变有在原肽序列中聚集的趋势。尽管遗传变体白蛋白长崎 - 3中的组氨酸 - 3被替换为谷氨酰胺会降低金属结合亲和力，但多肽链下游的突变没有这种作用，威尔逊病患者的白蛋白中铜结合亲和力也没有降低。
