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.

中文翻译：

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聚合层粘连蛋白在发育、健康和疾病中的作用


聚合层粘连蛋白是多结构域基底膜 (BM) 糖蛋白，可自组装成细胞锚定的平面晶格以建立初始 BM 支架。然后巢蛋白、IV 型胶原蛋白和蛋白多糖在不同的结构域位点结合到支架上，形成成熟的 BM。相邻层粘连蛋白的 LN 结构域相互结合形成聚合物节点，而 LG 结构域附着于细胞骨架锚定整合素和肌营养不良聚糖，以及脑硫苷脂和硫酸乙酰肝素。聚合物节点是聚合物支架的重复单元，被组织成近对称的三链节。最近通过冷冻电子显微镜结合 AlphaFold2 建模和生化研究解决了该结构，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（LN-核纤层蛋白病）中自组装失败。其中包括 LAMA2 相关营养不良和皮尔森综合征。