Xu L, Chen M, Peng J, O'Toole E A, Woodley D T, Chan L S
Department of Dermatology, Northwestern University Medical School, Tarry 4-721, Mail Code T225, 300 E. Superior Street, Chicago, IL 60611-3010, USA.
Biochim Biophys Acta. 1998 Oct 22;1408(1):25-34. doi: 10.1016/s0925-4439(98)00049-0.
Type VII collagen, the major component of anchoring fibrils, serves as tight adhesion of skin basement membrane zone (BMZ) through its amino-terminal non-collagenous (NC1) domain. The NC1 domain is targeted by autoantibodies of an acquired blistering skin disease termed epidermolysis bullosa acquisita (EBA) naturally occurring in humans and dogs. We cloned the full-length canine type VII collagen NC1 domain cDNA and delineated its molecular and immunological characteristics. The canine NC1 domain cDNA consists of 3759 nucleotides encoding for 1253 amino acids, with a molecular mass of approx. 134 kDa and a 17 amino acid signal peptide. The expression of canine type VII collagen was confirmed by Northern blot analysis and by a rabbit antibody raised against a 17 amino acid peptide deduced from canine NC1 sequence. Comparison of canine NC1 with the corresponding human sequence indicated 86.7% and 87.6% identity at the nucleotide and deduced amino acid levels respectively. The protein homology reached greater than 95% within two immunodominant epitope areas. Furthermore, human EBA autoantibodies and a rabbit anti-human NC1 cross-reacted with canine skin BMZ and the newly synthesized canine type VII collagen. The molecular and immunological identities between human and canine NC1 domains suggest that NC1 may be critical for the EBA development.
VII型胶原蛋白是锚定原纤维的主要成分，通过其氨基末端非胶原蛋白（NC1）结构域实现皮肤基底膜带（BMZ）的紧密黏附。NC1结构域是一种名为获得性大疱性表皮松解症（EBA）的获得性水疱性皮肤病的自身抗体的作用靶点，EBA在人和犬中自然发生。我们克隆了犬VII型胶原蛋白NC1结构域的全长cDNA，并描述了其分子和免疫学特征。犬NC1结构域cDNA由3759个核苷酸组成，编码1253个氨基酸，分子量约为134 kDa，还有一个17个氨基酸的信号肽。通过Northern印迹分析以及用针对从犬NC1序列推导的17个氨基酸肽产生的兔抗体，证实了犬VII型胶原蛋白的表达。犬NC1与相应人类序列的比较表明，在核苷酸水平和推导氨基酸水平上的同一性分别为86.7%和87.6%。在两个免疫显性表位区域内，蛋白质同源性超过95%。此外，人类EBA自身抗体和兔抗人NC1与犬皮肤BMZ以及新合成的犬VII型胶原蛋白发生交叉反应。人和犬NC1结构域之间的分子和免疫学同一性表明，NC1可能对EBA的发生发展至关重要。
