MUCIN GENES AND THE PROTEINS THEY ENCODE - STRUCTURE, DIVERSITY, AND REGULATION

MUCIN GENES AND THE PROTEINS THEY ENCODE - STRUCTURE, DIVERSITY, AND REGULATION
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DOI:
10.1165/ajrcmb/7.6.557
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发表时间:
1992-12-01
影响因子:
6.4
通讯作者:
GUM, JR
GUM, JR
中科院分区:
医学1区
文献类型:
--
作者:
GUM, JR

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粘蛋白是保护呼吸道、胃肠道和生殖道的粘液凝胶的结构组分。这些多分散糖蛋白(250,000至20,000,000 D)是基于质量的大约80%的碳水化合物,并且由于它们的大尺寸和极端亲水性而具有高特性粘度。负责这种亲水性的结构粘蛋白寡糖在大小和结构上是异质的,但主要是O-连接的,即,它们起始于连接到多肽骨架的苏氨酸和丝氨酸残基上的N-乙酰半乳糖胺残基。在过去的几年里,随着编码粘蛋白多肽骨架的cDNA克隆的分离和测序,我们对粘蛋白结构的理解迅速发展。所有目前良好表征的粘蛋白已被发现含有丰富的潜在O-糖基化位点的串联重复肽的扩展阵列。鲜为人知的是侧翼的分泌粘蛋白的串联重复序列阵列的独特序列,但目前可用的信息表明,这些侧翼区含有丰富的半胱氨酸的延伸,参与粘蛋白寡聚体的形成。因此,分泌性粘蛋白似乎由含有高度糖基化结构域的寡聚体组成,所述结构域两侧是聚合所需的独特序列。在描述编码粘蛋白的基因方面也取得了进展。目前已知的人类粘蛋白基因至少有四种,尽管还有许多其他的基因有待发现。此外,在我们了解粘蛋白基因表达及其组织特异性调控的机制之前,还有很多工作要做。
Mucins are the structural components of the mucus gels that protect the respiratory, gastrointestinal, and reproductive tracts. These polydispserse glycoproteins (250,000 to 20,000,000 D) are approximately 80% carbohydrate on a mass basis and have a high intrinsic viscosity due to their large size and extreme hydrophilicity. Mucin oligosaccharides, the structures responsible for this hydrophilicity, are heterogeneous in size and structure but are chiefly O-linked, i.e., they initiate from N-acetylgalactosamine residues attached to threonine and serine residues of the polypeptide backbone. Our understanding of the structure of mucins has advanced rapidly in the last few years with the isolation and sequencing of cDNA clones that encode mucin polypeptide backbones. All currently well-characterized mucins have been found to contain extended arrays of tandemly repeated peptides rich in potential O-glycosylation sites. Less is known about the unique sequences that flank the tandem repeat arrays of secretory mucins, but currently available information indicates that these flanking regions contain cysteine-rich stretches that participate in mucin oligomer formation. Thus, secretory mucins appear to consist of oligomers containing heavily glycosylated domains flanked by unique sequences required for polymerization. Progress has also been made in characterizing the genes that encode mucins. At least four human mucin genes are known at present, although many others may remain to be discovered. Moreover, much work remains before we gain an understanding of the mechanisms involved in the expression of mucin genes and their tissue-specific regulation.