Nguyen Q, Liu J, Roughley P J, Mort J S
Joint Diseases Laboratory, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada.
Biochem J. 1991 Aug 15;278 ( Pt 1)(Pt 1):143-7. doi: 10.1042/bj2780143.
The link protein components of proteoglycan aggregates in adult human articular cartilage show heterogeneity due to proteolysis. Cleavages near the N-terminus of the intact link proteins, before residues 17, 19 and 24, generate three proteins of slightly diminished size (LP3). Cleavages within the N-terminal disulphide-bonded loop, before residues 66 and 73 of the intact link proteins, generate proteins that yield smaller degradation products upon reduction (LP fragments). In vitro, modified link protein components of a similar size to LP3 can be generated by a variety of proteinases, but of the physiologically relevant enzymes only stromelysin, cathepsin B and cathepsin G have the ability to yield modified link proteins with N-termini identical with those observed in situ. None of the proteolytic agents tested was able to produce LP fragments with N-termini identical with those observed in situ, and the majority of proteinases were not able to cleave within the disulphide-bonded loops. Cathepsin L and hydroxyl radicals can cleave within the N-terminal disulphide-bonded loop, and have the potential of initially opening the loop to allow further proteolytic processing by other agents to generate the native cleavage sites.
由于蛋白水解作用，成年人类关节软骨中蛋白聚糖聚集体的连接蛋白成分呈现出异质性。在完整连接蛋白的N端附近，即在第17、19和24位残基之前发生切割，产生三种大小略有减小的蛋白（LP3）。在完整连接蛋白的第66和73位残基之前，在N端二硫键结合环内发生切割，产生在还原后会产生更小降解产物的蛋白（LP片段）。在体外，多种蛋白酶可产生与LP3大小相似的修饰连接蛋白成分，但在生理相关酶中，只有基质溶素、组织蛋白酶B和组织蛋白酶G有能力产生N端与原位观察到的相同的修饰连接蛋白。所测试的蛋白水解剂均不能产生N端与原位观察到的相同的LP片段，并且大多数蛋白酶不能在二硫键结合环内进行切割。组织蛋白酶L和羟基自由基可在N端二硫键结合环内进行切割，并有可能首先打开该环，以便其他试剂进一步进行蛋白水解加工，从而产生天然切割位点。
