Blumberg B, MacKrell A J, Fessler J H
Molecular Biology Institute, University of California, Los Angeles 90024.
J Biol Chem. 1988 Dec 5;263(34):18328-37.
A Drosophila melanogaster gene for a basement membrane procollagen chain was recently identified from the sequence homology of the carboxyl (NC1) end of the polypeptide that it encodes with the corresponding domain of human and murine collagens IV (Blumberg, B., MacKrell, A. J., Olson, P. F., Kurkinen, M., Monson, J. M., Natzle, J. E., and Fessler, J. H. (1987) J. Biol. Chem. 262, 5947-5950). This gene is at chromosome location 25C. Here we report the complete 6-kilobase cDNA sequence coding for a chain of 1775 amino acids, as well as the genomic structure. The gene is composed of nine relatively large exons separated by eight relatively small introns. This organization is different from the multiple small exons separated by large introns reported for mouse and human type IV collagens (Kurkinen, M., Bernard, M. P., Barlow, D. P., and Chow, L. T. (1985) Nature 317, 177-179. Sakurai, Y., Sullivan, M., and Yamada, Y. (1986) J. Biol. Chem. 261, 6654-6657. Soininen, R., Tikka, L., Chow, L., Pihlajaniemi, T., Kurkinen, M., Prockop, D. J., Boyd, C. D., and Tryggvason, K. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 1568-1572). Drosophila and human alpha 1(IV) procollagen chains share not only polypeptide domains near their amino and carboxyl ends for making specialized, intermolecular junctional complexes, but also 11 of 21 sites of imperfections of the collagen triple helix. However, neither the number nor the nature of the amino acids in these imperfections appear to have been conserved. These imperfections of the helical sequence may be important for the supramolecular assembly of basement membrane collagen. The 9 cysteine residues of the Drosophila collagen thread domain are arranged as several variations of a motif found in vertebrate collagens IV only near their amino ends, in their "7 S" junctional domains. The relative positions of these cysteine residues provide numerous opportunities for disulfide bonding between molecules in both parallel and antiparallel arrays. There is a pseudorepeat of one-third of the thread length, and there are numerous possibilities for disulfide-linked microfibrils and networks. We propose that collagen microfibrils, stabilized by disulfide segment junctions, are a versatile ancestral form from which specialized collagen fibers and networks arose.
最近，通过果蝇（Drosophila melanogaster）编码的多肽羧基（NC1）末端与人及小鼠IV型胶原蛋白相应结构域的序列同源性，鉴定出一种果蝇基底膜前胶原链基因（Blumberg, B., MacKrell, A. J., Olson, P. F., Kurkinen, M., Monson, J. M., Natzle, J. E., and Fessler, J. H. (1987) J. Biol. Chem. 262, 5947 - 5950）。该基因位于染色体25C位置。在此，我们报告了编码1775个氨基酸链的完整6千碱基cDNA序列以及基因组结构。该基因由9个相对较大的外显子和8个相对较小的内含子组成。这种结构组织与报道的小鼠和人类IV型胶原蛋白由多个被大内含子分隔的小外显子不同（Kurkinen, M., Bernard, M. P., Barlow, D. P., and Chow, L. T. (1985) Nature 317, 177 - 179. Sakurai, Y., Sullivan, M., and Yamada, Y. (1986) J. Biol. Chem. 261, 6654 - 6657. Soininen, R., Tikka, L., Chow, L., Pihlajaniemi, T., Kurkinen, M., Prockop, D. J., Boyd, C. D., and Tryggvason, K. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 1568 - 1572）。果蝇和人类α1(IV)前胶原链不仅在其氨基和羧基末端附近共享用于形成特殊分子间连接复合物的多肽结构域，而且在胶原蛋白三螺旋的21个不完善位点中有11个是相同的。然而，这些不完善位点中氨基酸的数量和性质似乎都没有保守下来。螺旋序列的这些不完善之处可能对基底膜胶原蛋白的超分子组装很重要。果蝇胶原蛋白螺纹结构域的9个半胱氨酸残基仅在其氨基末端附近、在它们的“7S”连接结构域中，以在脊椎动物IV型胶原蛋白中发现的一种基序的几种变体形式排列。这些半胱氨酸残基的相对位置为平行和反平行排列的分子之间的二硫键形成提供了许多机会。螺纹长度的三分之一存在假重复，并且存在许多形成二硫键连接的微纤维和网络的可能性。我们提出，由二硫键段连接稳定的胶原微纤维是一种通用的祖先形式，特殊的胶原纤维和网络由此产生。
