Peysselon Franck, Xue Bin, Uversky Vladimir N, Ricard-Blum Sylvie
Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS - Université Lyon 1, 7 Passage du Vercors, 69367 Lyon Cedex 07, France.
Mol Biosyst. 2011 Dec;7(12):3353-65. doi: 10.1039/c1mb05316g. Epub 2011 Oct 19.
The extracellular matrix is very well organized at the supramolecular and tissue levels and little is known on the potential role of intrinsic disorder in promoting its organization. We predicted the amount of disorder and identified disordered regions in the human extracellular proteome with established computational tools. The extracellular proteome is significantly enriched in proteins comprising more than 50% of disorder compared to the complete human proteome. The enrichment is mostly due to long disordered regions containing at least 100 consecutive disordered residues. The amount of intrinsic disorder is heterogeneous in the extracellular protein families, with the most disordered being collagens and the small integrin-binding ligand N-linked glycoproteins. Although most domains found in extracellular proteins are structured, the fibronectin III domains contain a variable amount of disordered residues (up to 92%). Binding sites for heparin and integrins are found in disordered sequences of extracellular proteins. Intrinsic disorder is evenly distributed in hubs and ends in the interaction network of extracellular proteins with their extracellular partners. In contrast, extracellular hubs are significantly enriched in disorder in the network of extracellular proteins with their extracellular, membrane and intracellular partners. Disorder could thus provide the structural plasticity required for the hubs to interact with membrane and intracellular proteins. Organization and assembly of the extracellular matrix, development of mineralized tissues and cell-matrix adhesion are the biological processes overrepresented in the most disordered extracellular proteins. Extracellular disorder is associated with binding to growth factors, glycosaminoglycans and integrins at the molecular level.
细胞外基质在超分子和组织水平上组织良好，而关于内在无序在促进其组织化过程中的潜在作用却知之甚少。我们使用已建立的计算工具预测了人类细胞外蛋白质组中的无序量并确定了无序区域。与完整的人类蛋白质组相比，细胞外蛋白质组中包含超过50%无序结构的蛋白质显著富集。这种富集主要归因于包含至少100个连续无序残基的长无序区域。细胞外蛋白质家族中内在无序的量是异质的，其中无序程度最高的是胶原蛋白和小整合素结合配体N-连接糖蛋白。尽管细胞外蛋白质中发现的大多数结构域是有序的，但纤连蛋白III结构域含有可变数量的无序残基（高达92%）。肝素和整合素的结合位点存在于细胞外蛋白质的无序序列中。内在无序在细胞外蛋白质与其细胞外伴侣的相互作用网络的中心和末端均匀分布。相比之下，在细胞外蛋白质与其细胞外、膜和细胞内伴侣的网络中，细胞外中心显著富集无序结构。因此，无序可能为中心与膜蛋白和细胞内蛋白相互作用提供所需的结构可塑性。细胞外基质的组织和组装、矿化组织的发育以及细胞与基质的粘附是在无序程度最高的细胞外蛋白质中过度表达的生物学过程。细胞外无序在分子水平上与生长因子、糖胺聚糖和整合素的结合相关。
