The structure and assembly of collagen VI using cryo-EM and SAXS

细胞外基质是在细胞外发现的所有物质，它构成了我们体内的大部分组织。基质由复杂的蛋白质网络组成，为细胞提供支持，为组织提供框架。大多数基质蛋白的结构和组织都很难理解，因为它们非常复杂，并且已经证明理解它们的组织是一个重大挑战。然而，新的方法现在开始揭示关于它们的组装和结构组织的重要信息。胶原VI微纤维是细胞外基质的重要组分。这些微纤维广泛分布于全身，在细胞和蛋白质之间形成许多连接。胶原VI的突变与遗传性肌营养不良症有关，这突出了研究这种分子的重要性。本研究的目的是利用低温电子显微镜技术研究VI型胶原微纤维的结构和功能。冷冻水合微纤丝的许多低对比度图像将被平均以产生3D结构。通过观察胶原VI蛋白的小片段的形状并将其映射到微纤维的3D结构上，将添加更多细节。我们还将研究类似于在人体组织中发现的晶格状结构中的VI型胶原蛋白的较大组装体。从这些数据中产生的结构将增加我们对这些复杂微纤维组织的理解。

The extracellular matrix is all the material that is found outside of the cell and it makes up most of the tissues in our bodies. The matrix is composed of an intricate network of proteins which provides support for cells and the framework for tissues. The structure and organisation of most matrix proteins is poorly understood as they are very complicated, and it has proved a major challenge to understand their organisation. However, new approaches are now beginning to reveal important information on their assembly and structural organisation. Collagen VI microfibrils are important components of the extracellular matrix. These microfibrils have widespread distributions throughout the body where they form many linkages between cells and proteins. Mutations in collagen VI are linked to inherited muscular dystrophies, highlighting how important it is to study this molecule. The aims of this project are to investigate the structure and function of collagen VI microfibrils using the technique of cryo-Electron Microscopy. Many low contrast images of frozen hydrated microfibrils will be averaged to produce a 3D structure. Further details will be added by looking at the shape of small fragments of the collagen VI protein and mapping these onto the 3D structure of the microfibril. We will also look at larger assemblies of collagen VI in lattice-like structures, similar to those found in human tissues. The structure produced from these data will increase our understanding of the organisation of these complicated microfibrils.