Center for Insoluble Protein Structures and Interdisciplinary Nanoscience Center at the Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.
Biochemistry. 2013 Apr 23;52(16):2821-7. doi: 10.1021/bi400212m. Epub 2013 Apr 15.
TGFBIp, also known as keratoepithelin and βig-h3, is among the most abundant proteins in the human cornea, and approximately 60% is associated with the insoluble fraction following extraction in sodium dodecyl sulfate (SDS) sample buffer. TGFBIp is of particular interest because a wide range of mutations causes amyloid or fuchsinophilic crystalloid deposits in the cornea leading to visual impairment. We show that the SDS-insoluble fraction of TGFBIp from porcine and human corneas is covalently linked via a reducible bond to the NC3 domain of type XII collagen in a TGFBIp:type XII collagen stoichiometric ratio of 2:1. Because type XII collagen is anchored to striated collagen fibers of the extracellular matrix, its interaction with TGFBIp is likely to provide anchoring for cells to the extracellular matrix through the integrin binding capability of TGFBIp. Furthermore, the TGFBIp-type XII collagen molecule will affect our understanding of the molecular pathogenesis of the TGFBI-linked corneal dystrophies.
TGFBIp，也被称为角蛋白上皮素和βig-h3，是人类角膜中含量最丰富的蛋白质之一，大约 60%的 TGFBIp 在十二烷基硫酸钠（SDS）样品缓冲液中提取后与不溶性部分相关。TGFBIp 特别有趣，因为广泛的突变会导致角膜中淀粉样或红染结晶状沉积物，从而导致视力损害。我们表明，来自猪和人角膜的 SDS 不溶性 TGFBIp 部分通过可还原键与 XII 型胶原的 NC3 结构域共价连接，形成 TGFBIp:type XII 胶原的比例为 2:1。由于 XII 型胶原锚定在细胞外基质的横纹胶原纤维上，因此它与 TGFBIp 的相互作用可能通过 TGFBIp 的整合素结合能力为细胞提供与细胞外基质的锚定。此外，TGFBIp- XII 型胶原分子将影响我们对与 TGFBI 相关的角膜营养不良的分子发病机制的理解。
