Sottrup-Jensen L, Sand O, Kristensen L, Fey G H
Department of Molecular Biology, University of Aarhus, Denmark.
J Biol Chem. 1989 Sep 25;264(27):15781-9.
The amino acid sequence of a 90-residue segment of human pregnancy zone protein containing its bait region has been determined. Human alpha 2-macroglobulin, human pregnancy zone protein, and rat alpha 1-macroglobulin, alpha 2-macroglobulin, and alpha 1-inhibitor 3 variants 1 and 2 constitute a group of homologous proteins; but the sequences of their bait regions are not related, and they differ in length (32-53 residues). The alpha-macroglobulin bait region is located equivalently with residues 666-706 in human alpha 2-macroglobulin. In view of the extreme sequence variation of the bait regions, the evolutionary constraints for these regions are likely to differ from those of the remainder of the alpha-macroglobulin structure. The sites of specific limited proteolysis in the bait regions of human pregnancy zone protein and rat alpha 1-macroglobulin, alpha 2-macroglobulin, and alpha 1-inhibitor 3 variants 1 and 2 by a variety of proteinases differing in specificity have been determined and compared with those identified earlier in human alpha 2-macroglobulin. The sites of cleavage generally conform to the substrate specificity of the proteinase in question, but the positions and nature of the P4-P4' sites differ. Most cleavages occur in two relatively small segments spaced by 6-10 residues; and in each case, bait region cleavage leads to alpha-macroglobulin-proteinase complex formation. The rate at which a given proteinase cleaves alpha-macroglobulin bait regions is likely to show great variation. Possible structural features of the widely different bait regions and their role in the mechanism of activation are discussed.
已确定人妊娠区蛋白包含其诱饵区的一段90个残基片段的氨基酸序列。人α2-巨球蛋白、人妊娠区蛋白以及大鼠α1-巨球蛋白、α2-巨球蛋白和α1-抑制剂3变体1和2构成一组同源蛋白；但它们诱饵区的序列不相关，且长度不同（32 - 53个残基）。α-巨球蛋白诱饵区在人α2-巨球蛋白中与666 - 706位残基位置相当。鉴于诱饵区序列的极端变异，这些区域的进化限制可能与α-巨球蛋白结构的其余部分不同。已确定并比较了人妊娠区蛋白以及大鼠α1-巨球蛋白、α2-巨球蛋白和α1-抑制剂3变体1和2的诱饵区被多种特异性不同的蛋白酶进行特异性有限蛋白水解的位点，这些位点与先前在人α2-巨球蛋白中鉴定出的位点进行了比较。切割位点通常符合所讨论蛋白酶的底物特异性，但P4 - P4'位点的位置和性质不同。大多数切割发生在两个间隔6 - 10个残基的相对较小片段中；并且在每种情况下，诱饵区切割都会导致α-巨球蛋白 - 蛋白酶复合物的形成。给定蛋白酶切割α-巨球蛋白诱饵区的速率可能会有很大差异。讨论了差异极大的诱饵区可能的结构特征及其在激活机制中的作用。
