Abstract：
Polymerizing laminins are multi-domain basement membrane (BM) glycoproteins that self-assemble into cell-anchored planar lattices to establish the initial BM scaffold. Nidogens, collagen-IV and proteoglycans then bind to the scaffold at different domain loci to create a mature BM. The LN domains of adjacent laminins bind to each other to form a polymer node, while the LG domains attach to cytoskeletal-anchoring integrins and dystroglycan, as well as to sulfatides and heparan sulfates. The polymer node, the repeating unit of the polymer scaffold, is organized into a near-symmetrical triskelion. The structure, recently solved by cryo-electron microscopy in combination with AlphaFold2 modeling and biochemical studies, reveals how the LN surface residues interact with each other and how mutations cause failures of self-assembly in an emerging group of diseases, the LN-lamininopathies, that include LAMA2-related dystrophy and Pierson syndrome.
摘要：
聚合层粘连蛋白是多结构域基底膜(BM)糖蛋白,其自组装成细胞锚定的平面晶格以建立初始BM支架。Nidogens,然后，胶原蛋白IV和蛋白聚糖在不同的结构域基因座处与支架结合以产生成熟的BM。相邻层粘连蛋白的LN结构域彼此结合形成聚合物节点，而LG结构域连接到细胞骨架锚定整合素和营养不良聚糖，以及硫酸盐和硫酸乙酰肝素。聚合物节点，聚合物支架的重复单元，被组织成一个近乎对称的triskelion.结构,最近通过冷冻电子显微镜结合AlphaFold2建模和生化研究解决，揭示了LN表面残基如何相互作用，以及突变如何导致一组新兴疾病中的自组装失败，LN-层粘连蛋白病,包括LAMA2相关的营养不良和Pierson综合征。
