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卡氏肺孢子虫主要表面糖蛋白的多基因家族:全长cDNA克隆与表达

Multi-gene family of major surface glycoproteins of Pneumocystis carinii: full-size cDNA cloning and expression.

作者信息

Kitada K, Wada M, Nakamura Y

机构信息

Department of Tumor Biology, University of Tokyo, Japan.

出版信息

DNA Res. 1994;1(2):57-66. doi: 10.1093/dnares/1.2.57.

DOI:10.1093/dnares/1.2.57
PMID:7584029
Abstract

The major surface glycoprotein (MSG) of Pneumocystis carinii plays a crucial role in the fatal pneumonia caused by this organism in AIDS patients. A cDNA encoding a full-length MSG polypeptide was isolated from a lambda library of rat-derived P. carinii cDNAs. The deduced MSG, referred to as the MSG5 subtype, is a 120,765-Da protein composed of 1,076 amino acids and contains an anchoring hydrophobic sequence at the C-terminus of the protein. Sequence analyses of cloned MSG-cDNAs revealed an MSG-gene family with approximately 70% protein sequence identity between subtypes. P. carinii karyotype hybridization analyses indicated that the MSG gene family members are scattered throughout most of the P. carinii chromosomes. These recombinant MSG proteins reacted with the antiserum from P. carinii-infected rats, as expected, and antiserum generated against P. carinii-infected mice, indicating the existence of common determinants in MSG polypeptides. The family of MSG proteins is rich in cysteine residues and these cysteines are highly conserved in all MSG subtypes regardless of species specificity, suggesting the structural and/or functional importance of these cysteines. The pathobiological significance of the MSG gene family and its sequence diversity in P. carinii is discussed.

摘要

卡氏肺孢子虫的主要表面糖蛋白(MSG)在该病原体导致艾滋病患者发生致命性肺炎的过程中起着关键作用。从大鼠来源的卡氏肺孢子虫cDNA的λ文库中分离出一个编码全长MSG多肽的cDNA。推导的MSG,称为MSG5亚型,是一种由1076个氨基酸组成的120,765道尔顿的蛋白质,在蛋白质的C末端含有一个锚定疏水序列。对克隆的MSG-cDNA的序列分析揭示了一个MSG基因家族,各亚型之间的蛋白质序列同一性约为70%。卡氏肺孢子虫核型杂交分析表明,MSG基因家族成员分散在卡氏肺孢子虫的大部分染色体上。这些重组MSG蛋白与来自感染卡氏肺孢子虫的大鼠的抗血清以及针对感染卡氏肺孢子虫的小鼠产生的抗血清发生反应,这表明MSG多肽中存在共同的决定簇。MSG蛋白家族富含半胱氨酸残基,并且这些半胱氨酸在所有MSG亚型中高度保守,与物种特异性无关,这表明这些半胱氨酸在结构和/或功能上具有重要性。本文讨论了MSG基因家族及其序列多样性在卡氏肺孢子虫中的病理生物学意义。

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