GENOMIC ORGANIZATION OF THE SEQUENCE CODING FOR FIBRILLIN, THE DEFECTIVE GENE-PRODUCT IN MARFAN-SYNDROME
GENOMIC ORGANIZATION OF THE SEQUENCE CODING FOR FIBRILLIN, THE DEFECTIVE GENE-PRODUCT IN MARFAN-SYNDROME
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DOI：
10.1093/hmg/2.7.961
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发表时间：
1993-07-01
影响因子：
3.5
通讯作者：
BONADIO, J
中科院分区：
文献类型：
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作者：
PEREIRA, L;DALESSIO, M;BONADIO, J
马凡氏综合征是由细胞外基质糖蛋白突变引起的。先前的研究已经表征了大约6.9 kb的估计10 kb的转录本。我们现在已经完成了的一级结构，阐明了外显子/内含子组织的基因，并得出了物理地图的遗传位点。Pre-tuberin由2，871个氨基酸组成，除了信号肽外，排列成五个结构不同的区域。这些区域中最大的区域占整个蛋白质的约75%，并且由与表皮生长因子（EGF）和转化生长因子-β结合蛋白（TGF-β）的肽基序同源的许多重复的富含半胱氨酸的序列组成。46个EGF样重复序列中的43个含有钙结合共有序列（EGF-CB），可以想象其介导蛋白质-蛋白质相互作用。原纤蛋白具有一些额外的富含半胱氨酸的模块，这些模块显然是这种大分子所独有的，并且可能代表EGF-CB和TGF-bp基序的进化变体。几乎所有的富含半胱氨酸的重复序列都是由单个外显子编码的;因此，Escherin基因相对较大（约110-kb）且高度片段化（65个外显子）。这项研究提供了第一个全面的分析，马凡氏综合征突变的充分表征的基因和相关信息。
Marfan syndrome results from mutations in an extracellular matrix glycoprotein, fibrillin. Previous studies have characterized approximately 6.9-kb of the estimated 10-kb fibrillin transcript. We have now completed the primary structure of fibrillin, elucidated the exon/intron organization of the gene and derived a physical map of the genetic locus. Pre-fibrillin consists of 2,871 amino acids which, excluding the signal peptide, are arranged into five structurally distinct regions. The largest of these regions comprises about 75% of the entire protein and consists of numerous repeated cysteine-rich sequences homologous to the peptide motifs of the epidermal growth factor (EGF) and transforming growth factor-beta binding protein (TGF-bp). Forty-three of the forty-six EGF-like repeats contain a calcium binding consensus sequence (EGF-CB) conceivably mediating protein-protein interactions. Fibrillin exhibits a few additional cysteine-rich modules that are apparently unique to this macromolecule and may represent evolutionary variants of the EGF-CB and TGF-bp motifs. Almost all of the cysteine-rich repeats are encoded by single exons; consequently, the fibrillin gene is relatively large (approximately 110-kb) and highly fragmented (65 exons). This study provides the first comprehensive analysis of the fibrillin gene and relevant information for the full characterization of Marfan syndrome mutations.