Interactions between the cartilage oligomeric matrix protein and matrilins. Implications for matrix assembly and the pathogenesis of chondrodysplasias.
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| Abstract |
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 coretained in the rough endoplasmatic reticulum where COMP accumulates in the chondrocytes of patients.
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| Authors | Henning H Mann, Suat Ozbek, Jürgen Engel, Mats Paulsson, Raimund Wagener |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 24 Pg. 25294-8 (Jun 11 2004) ISSN: 0021-9258 [Print] United States |
| PMID | 15075323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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