Gara Sudheer Kumar, Grumati Paolo, Urciuolo Anna, Bonaldo Paolo, Kobbe Birgit, Koch Manuel, Paulsson Mats, Wagener Raimund
Center for Biochemistry, Center for Molecular Medicine, and Department of Dermatology, Medical Faculty, University of Cologne, D-50931 Cologne, Germany.
J Biol Chem. 2008 Apr 18;283(16):10658-70. doi: 10.1074/jbc.M709540200. Epub 2008 Feb 13.
Here we describe three novel collagen VI chains, alpha4, alpha5, and alpha6. The corresponding genes are arranged in tandem on mouse chromosome 9. The new chains structurally resemble the collagen VI alpha3 chain. Each chain consists of seven von Willebrand factor A domains followed by a collagenous domain, two C-terminal von Willebrand factor A domains, and a unique domain. In addition, the collagen VI alpha4 chain carries a Kunitz domain at the C terminus, whereas the collagen VI alpha5 chain contains an additional von Willebrand factor A domain and a unique domain. The size of the collagenous domains and the position of the structurally important cysteine residues within these domains are identical between the collagen VI alpha3, alpha4, alpha5, and alpha6 chains. In mouse, the new chains are found in or close to basement membranes. Collagen VI alpha1 chain-deficient mice lack expression of the new collagen VI chains implicating that the new chains may substitute for the alpha3 chain, probably forming alpha1alpha2alpha4, alpha1alpha2alpha5, or alpha1alpha2alpha6 heterotrimers. Due to a large scale pericentric inversion, the human COL6A4 gene on chromosome 3 was broken into two pieces and became a non-processed pseudogene. Recently COL6A5 was linked to atopic dermatitis and designated COL29A1. The identification of novel collagen VI chains carries implications for the etiology of atopic dermatitis as well as Bethlem myopathy and Ullrich congenital muscular dystrophy.
在此，我们描述了三种新的胶原蛋白VI链，即α4、α5和α6。相应的基因在小鼠9号染色体上串联排列。这些新链在结构上类似于胶原蛋白VI的α3链。每条链都由七个血管性血友病因子A结构域、一个胶原结构域、两个C端血管性血友病因子A结构域和一个独特结构域组成。此外，胶原蛋白VI的α4链在C端带有一个Kunitz结构域，而胶原蛋白VI的α5链包含一个额外的血管性血友病因子A结构域和一个独特结构域。胶原蛋白VI的α3、α4、α5和α6链的胶原结构域大小以及这些结构域内结构重要的半胱氨酸残基的位置是相同的。在小鼠中，这些新链存在于基底膜中或其附近。缺乏胶原蛋白VIα1链的小鼠缺乏这些新胶原蛋白VI链的表达，这意味着这些新链可能替代α3链，可能形成α1α2α4、α1α2α5或α1α2α6异源三聚体。由于大规模的着丝粒周围倒位，3号染色体上的人类COL6A4基因被分成两段，成为一个未加工的假基因。最近，COL6A5与特应性皮炎相关，并被命名为COL29A1。新胶原蛋白VI链的鉴定对特应性皮炎以及Bethlem肌病和Ullrich先天性肌营养不良的病因学具有重要意义。
