Supramolecular interactions in the dermo-epidermal junction zone - Anchoring fibril-collagen VII tightly binds to banded collagen fibrils
Supramolecular interactions in the dermo-epidermal junction zone - Anchoring fibril-collagen VII tightly binds to banded collagen fibrils
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DOI：
10.1074/jbc.m802415200
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发表时间：
2008-09-05
影响因子：
4.8
通讯作者：
Bruckner, Peter
中科院分区：
文献类型：
--
作者：
Villone, Daniela;Fritsch, Anja;Bruckner, Peter
正常人皮肤的真皮和表皮在功能上被基底膜分开，但一起形成稳定的结构连续体。包围原纤维通过插入基底膜和插入乳头状真皮的带状胶原原纤维来加强这种连接。胶原蛋白VII（锚定原纤维的主要分子成分）的结构异常导致与皮肤起泡相关的先天性皮肤脆性病症、营养不良性大疱性表皮病。在这里，我们的特点是锚定纤维和带状胶原纤维之间的相互作用的分子基础。真皮-表皮交界区的超结构片段通过机械破坏和磁性免疫珠分离产生。血管原纤维与带状胶原原纤维紧密连接。体外结合研究表明，胶原蛋白VII中的血管性血友病因子A样基序对于锚定原纤维与重构胶原蛋白I原纤维的结合是必不可少的。由于据报道胶原蛋白I和VII分子仅经历弱相互作用，因此锚定原纤维与胶原蛋白原纤维的附着取决于其组分的超分子组织。该复合物在原位稳定，并抵抗强变性剂的解离。
The dermis and the epidermis of normal human skin are functionally separated by a basement membrane but, together, form a stable structural continuum. Anchoring fibrils reinforce this connection by insertion into the basement membrane and by intercalation with banded collagen fibrils of the papillary dermis. Structural abnormalities in collagen VII, the major molecular constituent of anchoring fibrils, lead to a congenital skin fragility condition, dystrophic epidermolysis bullosa, associated with skin blistering. Here, we characterized the molecular basis of the interactions between anchoring fibrils and banded collagen fibrils. Suprastructural fragments of the dermo-epidermal junction zone were generated by mechanical disruption and by separation with magnetic Immunobeads. Anchoring fibrils were tightly attached to banded collagen fibrils. In vitro binding studies demonstrated that a von Willebrand factor A-like motif in collagen VII was essential for binding of anchoring fibrils to reconstituted collagen I fibrils. Since collagen I and VII molecules reportedly undergo only weak interactions, the attachment of anchoring fibrils to collagen fibrils depends on supramolecular organization of their constituents. This complex is stabilized in situ and resists dissociation by strong denaturants.