Interactions between the cartilage oligomeric matrix protein and matrilins -: Implications for matrix assembly and the pathogenesis of chondrodysplasias
Interactions between the cartilage oligomeric matrix protein and matrilins -: Implications for matrix assembly and the pathogenesis of chondrodysplasias
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DOI：
10.1074/jbc.m403778200
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发表时间：
2004-06-11
影响因子：
4.8
通讯作者：
Wagener, R
中科院分区：
文献类型：
--
作者：
Mann, HH;Özbek, S;Wagener, R
软骨寡聚基质蛋白（COMP）和基质蛋白是软骨细胞外基质中丰富的非胶原蛋白。在钙的存在下，COMP和matrilin-1在凝胶过滤软骨提取物中结合在一起，并可被免疫共沉淀。在筛选matrilin-1，-3，和-4的配体使用ELISA式的结合试验，COMP被确定为一个突出的结合伙伴的所有三个，表明保守的COMP之间的matrilin的相互作用。COMP和matrilin-4的相互作用是可饱和的，并且确定了1 nM的表观K-D。然而，只有全长COMP和全长matrilin-4蛋白显示出强烈的相互作用，表明寡聚体结构显著增加亲和力。COMP或matrilin-3的突变导致相关形式的人类软骨发育不良，并且在假性软骨发育不全患者中发现的COMP突变D469 Delta已被证明导致钙结合减少。尽管如此，该突变仅导致matrilin-4结合的轻微降低。这表明COMP与基质蛋白的结合受损不会导致假性软骨发育不全表型，而是基质蛋白可能共同保留在粗糙内质网中，其中COMP在患者的软骨细胞中积累。
The cartilage oligomeric matrix protein (COMP) and matrilins are abundant non-collagenous proteins in the cartilage extracellular matrix. In the presence of calcium, COMP and matrilin-1 elute together in the gel filtration of cartilage extracts and can be co-immunoprecipitated. In a screen for ligands of matrilin-1, -3, and -4 using an ELISA-style binding assay, COMP was identified as a prominent binding partner for all three, indicating a conservation of the COMP interaction among matrilins. The interaction of COMP and matrilin-4 is saturable, and an apparent K-D of 1 nM was determined. However, only the full-length COMP and the full-length matrilin-4 proteins showed a strong interaction, indicating that the oligomeric structures markedly increase the affinity. Mutations in COMP or matrilin-3 cause related forms of human chondrodysplasia, and the COMP mutation D469Delta, which is found in patients with pseudoachondroplasia, has been shown to cause a reduced calcium binding. Despite this, the mutation causes only a slight decrease in matrilin-4 binding. This indicates that impaired binding of COMP to matrilins does not cause the pseudoachondroplasia phenotype but rather that matrilins may be co-retained in the rough endoplasmatic reticulum where COMP accumulates in the chondrocytes of patients.