Heterogeneity of Collagen VI Microfibrils: STRUCTURAL ANALYSIS OF NON-COLLAGENOUS REGIONS.
Heterogeneity of Collagen VI Microfibrils: STRUCTURAL ANALYSIS OF NON-COLLAGENOUS REGIONS.
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DOI：
10.1074/jbc.m115.705160
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发表时间：
2016-03-04
期刊：
影响因子：
--
通讯作者：
Wagener R
中科院分区：
文献类型：
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作者：
Maaß T;Bayley CP;Mörgelin M;Lettmann S;Bonaldo P;Paulsson M;Baldock C;Wagener R
VI型胶原是一种胶原，其N端和C端的非胶原区非常大，在大多数结缔组织中形成了一个独特的微纤维网络。长期以来，它被认为由三条不同的α链(α1、α2和α3)组成。在细胞内，异三聚体分子结合形成二聚体和四聚体，然后分泌并组装成微纤维。三条新的VI型胶原α长链α4、α5和α6的鉴定引发了这样一个问题：在VI型胶原组装中，它们是否以及如何替代α3长链。在这里，我们研究了新的长链的结构特征，并分析了这些长链组装成四聚体和微纤维的过程。用小角X射线散射(SAXS)对VI型胶原N-端和C-端球状区进行了重组表达和研究。α4、α5和α6链的N-末端球状区的从头算模型显示出与α3链相似的C型结构。α-4链N-末端球状区的单颗粒EM纳米结构证实了SAXS揭示的C型结构。从组织中提取的VI型胶原的免疫-EM显示，与α3链一样，新的长链组装成同质异构体，并被结合到混合的微纤维中。此外，还建立了α1、α2、α4和α6链的C-末端球状区的SAXS模型。有趣的是，α1、α2和α4的C末端球状区域二聚化。这些自身相互作用可能在四聚体的形成中起作用。
Collagen VI, a collagen with uncharacteristically large N- and C-terminal non-collagenous regions, forms a distinct microfibrillar network in most connective tissues. It was long considered to consist of three genetically distinct α chains (α1, α2, and α3). Intracellularly, heterotrimeric molecules associate to form dimers and tetramers, which are then secreted and assembled to microfibrils. The identification of three novel long collagen VI α chains, α4, α5, and α6, led to the question if and how these may substitute for the long α3 chain in collagen VI assembly. Here, we studied structural features of the novel long chains and analyzed the assembly of these into tetramers and microfibrils. N- and C-terminal globular regions of collagen VI were recombinantly expressed and studied by small angle x-ray scattering (SAXS). Ab initio models of the N-terminal globular regions of the α4, α5, and α6 chains showed a C-shaped structure similar to that found for the α3 chain. Single particle EM nanostructure of the N-terminal globular region of the α4 chain confirmed the C-shaped structure revealed by SAXS. Immuno-EM of collagen VI extracted from tissue revealed that like the α3 chain the novel long chains assemble to homotetramers that are incorporated into mixed microfibrils. Moreover, SAXS models of the C-terminal globular regions of the α1, α2, α4, and α6 chains were generated. Interestingly, the α1, α2, and α4 C-terminal globular regions dimerize. These self-interactions may play a role in tetramer formation.