COOH-TERMINAL PROPEPTIDES OF THE MAJOR HUMAN PROCOLLAGENS - STRUCTURAL, FUNCTIONAL AND GENETIC COMPARISONS
COOH-TERMINAL PROPEPTIDES OF THE MAJOR HUMAN PROCOLLAGENS - STRUCTURAL, FUNCTIONAL AND GENETIC COMPARISONS
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DOI：
10.1016/0022-2836(87)90632-2
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发表时间：
1987-01-05
影响因子：
5.6
通讯作者：
MYERS, JC
中科院分区：
文献类型：
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作者：
DION, AS;MYERS, JC
人类所有主要前胶原的至少一条链的羧基末端延伸(COOH-前肽)的序列最近才被推导出来，包括间质(α1(I)、α2(I)、αI(II)、αI(III))、基底膜(α1(IV))和细胞周围(α2(V))前胶原的序列。对与这些COOH-前肽结构域相对应的DNA和蛋白质序列的比较，证实了基底膜α1(IV)COOH-前肽与间质和细胞周前胶原蛋白的相应序列的早期差异。后者相对保守，具有58%的初级肽序列相似性，而与α1(IV)的序列相似性有限。亲水性图谱和二级结构势进一步强调了细胞间质和细胞周围COOH-前肽之间的保守和可变区的聚集，并为这些序列与α1(IV)COOH-前肽之间的显著结构差异提供了进一步的证据。α1(I)、α2(I)、α1(II)、αI(III)和α2(V)COOH-前肽的最高度保守的序列包括碳水化合物结合位点周围的区域、半胱氨酸区和COOH-末端序列。半胱氨基、酪氨基和色氨酸残基与大多数带电残基一样高度保守。可变区的定位通常发生在内含子/外显子剪接连接附近具有高β转角电位的亲水序列中。预测二级结构分析表明，变异最大的序列与COOH-前肽的端肽和邻接的NH2-末端部分有关。这些结果，结合对异常α2(I)COOH-前肽(成骨不完善)的类似分析，使我们能够识别可能是COOH-前肽功能的先决条件的子序列，即三螺旋形成的前胶原链识别和成核位置。这些功能对α1(IV)COOH-前肽也是共同的；然而，该区域缺乏切割以及它在细胞外基质相互作用中的额外结构作用可能是其一级和二级结构不同的原因。
The sequences of the carboxy-terminal extensions (COOH-propeptides) of at least one chain of all of the major human procollagens have only recently been deduced, and include those of the interstitial (.alpha.1(I), .alpha.2(I), .alpha.I(II), .alpha.I(III)), basement membrane (.alpha.1(IV)) and pericellular (.alpha.2(V)) procollagens. Comparisons of DNA and protein sequences, corresponding to these COOH-propeptides domains, established the early divergence of the basement membrane .alpha.1(IV) COOH-propeptide from the corresponding sequences of the interstitial and pericellular procollagens. The latter are relatively highly conserved and share 58% primary peptide sequence similarities, whereas sequence similarities relative to .alpha.1(IV) are limited. Hydropathy profiles and secondary structure potentials further emphasize the clustering of conserved and variable regions among the interstitial and pericellular COOH-propeptides and provided further evidence for significant structural differences between these sequences and the .alpha.1(IV) COOH-propeptide. The most highly conserved sequences of the .alpha.1(I), .alpha.2(I), .alpha.1(II), .alpha.I(III) and .alpha.2(V) COOH-propeptides include regions surrounding the carbohydrate attachment site, cysteine-containing regions and the COOH-terminal sequences. Cysteinyl, tyrosyl and tryptophanyl residues were found to be highly conserved as were most charged residues. Localization of variable regions, in general, occurs within hydrophilic sequences with high .beta.-turn potentials that are proximal to intron/exon splice junctions. The most variable sequences are associated with the telopeptides and adjoining NH2-terinal portions of the COOH-propeptides as demonstrated by predictive secondary structure analyses. These results, combined with similar analyses of abnormal .alpha.2(I) COOH-propeptide (osteogenesis imperfecta) permitted the identification of subsequences that are likely to be a prerequisite for COOH-propeptide functions, namely procollagen chain recognition and nucleation sites for triple helix formation. These functions are also common to the .alpha.1(IV) COOH-propeptide; however, the lack of cleavage of this region and its additional postulated structural role in extracellular matrix interactions likely account for its divergent primary and secondary structure.