Hardingham T E, Fosang A J, Dudhia J
Kennedy Institute of Rheumatology, Hammersmith, London, UK.
Eur J Clin Chem Clin Biochem. 1994 Apr;32(4):249-57.
Aggrecan, the large aggregating proteoglycan from cartilage contains chondroitin sulphate and keratan sulphate attached to a multidomain protein core. It aggregates by binding to hyaluronan and this is further stabilised by a separate globular link protein. There are two structurally related N-terminal globular domains, G1 and G2, of which only G1 and not G2 is involved in aggregation. The interglobular domain joining G1 and G2 contains proteinase sensitive sequences which appear to be the key site for cleavage during aggrecan turnover. Much of the keratan sulphate and all of the chondroitin sulphate is attached to the long extended glycosaminoglycan attachment region. The function of the C-terminal G3 domain is unknown. It contains a mammalian type C lectin and complement regulatory protein motifs. These may have interactive properties that contribute to matrix organisation. There is also an alternatively spliced form with an epidermal growth factor-like motif. The carbohydrate composition of aggrecan varies with cartilage source, development and age and is heterogeneous in each sample. There is evidence of a close control of chondroitin sulphate synthesis that determines chain length and disaccharide composition and which change during development and in pathology. Monoclonal antibodies that recognise specific sequences within chondroitin sulphate chains enable some of these changes in fine structure to be detected. Progressive digestion of chains with chondroitinase AC II has provided evidence of a pattern of sulphation, with 6-sulphated disaccharides more abundant towards the protein core, although the disaccharide next to the linkage region is predominantly non-sulphated.
聚集蛋白聚糖是一种来自软骨的大型聚集蛋白聚糖，它含有连接在多结构域蛋白核心上的硫酸软骨素和硫酸角质素。它通过与透明质酸结合而聚集，并且这一过程通过一种单独的球状连接蛋白进一步稳定。有两个结构相关的N端球状结构域，即G1和G2，其中只有G1而非G2参与聚集。连接G1和G2的球状间结构域包含蛋白酶敏感序列，这些序列似乎是聚集蛋白聚糖周转过程中裂解的关键位点。大部分硫酸角质素和所有硫酸软骨素都连接在长延伸的糖胺聚糖附着区域。C端G3结构域的功能尚不清楚。它包含一个哺乳动物C型凝集素和补体调节蛋白基序。这些可能具有有助于基质组织的相互作用特性。还有一种具有表皮生长因子样基序的可变剪接形式。聚集蛋白聚糖的碳水化合物组成随软骨来源、发育和年龄而变化，并且在每个样本中都是异质的。有证据表明对硫酸软骨素合成有密切控制，这种控制决定了链长和二糖组成，并且在发育和病理过程中会发生变化。识别硫酸软骨素链内特定序列的单克隆抗体能够检测到这些精细结构中的一些变化。用硫酸软骨素酶AC II对链进行逐步消化提供了硫酸化模式的证据，6-硫酸化二糖在靠近蛋白核心处更为丰富，尽管连接区域旁边的二糖主要是非硫酸化的。
