Department of Biology, Copenhagen University, Copenhagen N, Denmark.
J Histochem Cytochem. 2012 Dec;60(12):987-96. doi: 10.1369/0022155412464376. Epub 2012 Sep 26.
The aggregating proteoglycans of the lectican family are important components of extracellular matrices. Aggrecan is the most well studied of these and is central to cartilage biomechanical properties and skeletal development. Key to its biological function is the fixed charge of the many glycosaminoglycan chains, that provide the basis for the viscoelastic properties necessary for load distribution over the articular surface. This review is focused on the globular domains of aggrecan and their role in anchoring the proteoglycans to other extracellular matrix components. The N-terminal G1 domain is vital in that it binds the proteoglycan to hyaluronan in ternary complex with link protein, retaining the proteoglycan in the tissue. The importance of the C-terminal G3 domain interactions has recently been emphasized by two different human hereditary disorders: autosomal recessive aggrecan-type spondyloepimetaphyseal dysplasia and autosomal dominant familial osteochondritis dissecans. In these two conditions, different missense mutations in the aggrecan C-type lectin repeat have been described. The resulting amino acid replacements affect the ligand interactions of the G3 domain, albeit with widely different phenotypic outcomes.
聚集蛋白聚糖是 lectican 家族的重要组成部分，是细胞外基质的重要组成部分。聚集蛋白聚糖是其中研究最为广泛的一种，它是软骨生物力学特性和骨骼发育的核心。其生物学功能的关键是许多糖胺聚糖链的固定电荷，这些电荷为关节表面的负荷分布提供了必要的粘弹性基础。本篇综述重点介绍了聚集蛋白聚糖的球形结构域及其在将蛋白聚糖锚定到其他细胞外基质成分中的作用。N 端 G1 结构域在将蛋白聚糖与透明质酸结合方面起着至关重要的作用，它与链接蛋白形成三元复合物，将蛋白聚糖保留在组织中。最近，两种不同的人类遗传性疾病——常染色体隐性遗传型聚集蛋白聚糖型脊椎骨骺发育不良和常染色体显性家族性骨软骨炎——强调了 C 端 G3 结构域相互作用的重要性。在这两种情况下，已在聚集蛋白聚糖 C 型凝集素重复序列中描述了不同的错义突变。由此产生的氨基酸取代会影响 G3 结构域的配体相互作用，但表型结果差异很大。
