CLONING AND PRIMARY STRUCTURAL-ANALYSIS OF THE BULLOUS PEMPHIGOID AUTOANTIGEN BP180
CLONING AND PRIMARY STRUCTURAL-ANALYSIS OF THE BULLOUS PEMPHIGOID AUTOANTIGEN BP180
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DOI：
10.1111/1523-1747.ep12616580
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发表时间：
1992-09-01
影响因子：
6.5
通讯作者：
DIAZ, LA
中科院分区：
文献类型：
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作者：
GIUDICE, GJ;EMERY, DJ;DIAZ, LA
大疱性类天疱疮。(BP)是一种自身免疫性皮肤病，其特征在于存在表皮下水疱，所述水疱由基底角质形成细胞和皮肤基底膜之间的粘附相互作用的破坏引起。来自患有这种疾病的患者的自身抗体识别两种表皮抗原，BP 180和BP 230，这两种抗原都定位于半桥粒，半桥粒是复层鳞状上皮的跨膜结构，在细胞-基质粘附中起作用。在本研究中，我们报告了一级结构分析的基础上的一系列重叠的cDNA克隆，包括4,669个碱基的BP 180转录本的序列。使用基于聚合酶链反应的方案来确认cDNA片段的连续性。 发现BP 180转录物的该克隆部分含有一个长的开放阅读框（ORF），长度为4，596个碱基。该ORF编码155，000道尔顿的多肽，等电点为9.7。BP 180的羧基末端的一半，916个氨基酸的延伸，由15个可变长度的胶原结构域（15至242个氨基酸）组成，其通过非胶原序列的短延伸彼此分开。位于胶原区上游76个氨基酸处的是一个假定的跨膜结构域，这是一种将BP 180与胶原家族所有充分表征的成员区分开的结构特征。该跨膜结构域被预测作为信号锚定序列发挥作用，将该蛋白质的C-末端胶原片段引导至细胞外部。推定的细胞内结构域是高度碱性的，等电点为10.37。该分子分析预测BP 180抗原是半桥粒的一种完整的膜蛋白，其含有长的细胞外胶原尾。这种结构特征的组合表明BP 180可能作为细胞-基质粘附分子发挥作用，胶原区域作为与基底膜组分相互作用的潜在位点。自身抗体介导的这种粘附相互作用的破坏可能在BP患者的表皮下水疱的发展中发挥关键作用。
Bullous pemphigoid. (BP) is an autoimmune skin disease that is characterized by the presence of subepidermal blisters resulting from a disruption of the adhesive interactions between basal keratinocytes and the cutaneous basement membrane. Autoantibodies from patients suffering from this disorder recognize two epidermal antigens, BP180 and BP230, both of which have been localized to the hemidesmosome, a transmembrane structure of stratified, squamous epithelia that functions in cell-matrix adhesion. In the present study we report the primary structural analysis of BP180 based on the sequence of a series of overlapping cDNA clones encompassing 4,669 bases of the BP180 transcript. A polymerase chain reaction-based protocol was used to confirm the contiguity of the cDNA segments. This cloned portion of the BP 1 80 transcript was found to contain one long open reading frame (ORF) 4,596 bases in length. This ORF encodes a polypeptide of 155,000 Daltons with an isoelectric point of 9.7. The carboxyl-terminal half of BP180, a stretch of 916 amino acids, consists of 15 collagen domains of variable length (1 5 to 242 amino acids) that are separated from one another by short stretches of non-collagen sequences. Located 76 amino acids upstream of the collagenous region is a putative transmembrane domain, a structural feature that distinguishes BP180 from all of the well-characterized members of the collagen family. This membrane-spanning domain is predicted to function as a signal-anchor sequence, directing the C-terminal collagenous segment of this protein to the exterior of the cell. The putative intracellular domain is highly basic with an isoelectric point of 10.37. This molecular analysis predicts that the BP180 antigen is an integral membrane protein of the hemidesmosome that contains a long extracellular collagenous tail. This combination of structural features suggests that BP180 may function as a cell-matrix adhesion molecule, with the collagenous region acting as a potential site of interaction with basement membrane components. Autoantibody-mediated disruption of such an adhesive interaction may play a critical role in the development of sub-epidermal blisters in BP patients.