Molecular Properties of Matrilin-3 Isolated from Human Growth Cartilage

Kleemann-Fischer, Doris; Kleemann, Gerd R.; Engel, D.; Yates, John R.; Wu, Jiann-Jiu; Eyre, David R.

doi:10.1006/abbi.2000.2256

Cited by 19 publications

(15 citation statements)

References 37 publications

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“…Matrilin-1 is expressed predominantly in cartilage, in particular the growth plate and articular cartilages, and co-localizes with matrilin-3 with which it can form hetero-oligomers (4, 5). Matrilin-1 is primarily expressed in the maturation zone of the growth plate, whereas matrilin-3 is found mainly in the proliferation zone (6, 7). …”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Investigations of Matrilin-1 A-domains Reveal Insights into Their Role in Cartilage ECM Assembly*

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Jowitt

Stephen

et al. 2010

Journal of Biological Chemistry

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Matrilin-1 is expressed predominantly in cartilage and co-localizes with matrilin-3 with which it can form hetero-oligomers. We recently described novel structural and functional features of the matrilin-3 A-domain (M3A) and demonstrated that it bound with high affinity to type II and IX collagens. Interactions preferentially occurred in the presence of Zn2+ suggesting that matrilin-3 has acquired a requirement for specific metal ions for activation and/or molecular associations. To understand the interdependence of matrilin-1/-3 hetero-oligomers in extracellular matrix (ECM) interactions, we have extended these studies to include the two matrilin-1 A-domains (i.e. M1A1 and M1A2 respectively). In this study we have identified new characteristics of the matrilin-1 A-domains by describing their glycosylation state and the effect of N-glycan chains on their structure, thermal stability, and protein-protein interactions. Initial characterization revealed that N-glycosylation did not affect secretion of these two proteins, nor did it alter their folding characteristics. However, removal of the glycosylation decreased their thermal stability. We then compared the effect of different cations on binding between both M1A domains and type II and IX collagens and showed that Zn2+ also supports their interactions. Finally, we have demonstrated that both M1A1 domains and biglycan are essential for the association of the type II·VI collagen complex. We predict that a potential role of the matrilin-1/-3 hetero-oligomer might be to increase multivalency, and therefore the ability to connect various ECM components. Differing affinities could act to regulate the integrated network, thus coordinating the organization of the macromolecular structures in the cartilage ECM.

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Section: Introductionmentioning

confidence: 99%

Structural and Functional Investigations of Matrilin-1 A-domains Reveal Insights into Their Role in Cartilage ECM Assembly*

Fresquet

Jowitt

Stephen

et al. 2010

Journal of Biological Chemistry

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“…A second vWFA domain, present in the other matrilins between the EGF-like domains and the coiled-coil domain, is absent. Matrilin-3 can form homotetramers via the coiled-coil domain (16), and in addition, mixed trimers and tetramers of matrilin-3 and matrilin-1 have been observed in human (19) and calf (16,32), whereas these heterooligomers could not be identified in mouse (3).…”

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confidence: 98%

Matrilin-3 Is Dispensable for Mouse Skeletal Growth and Development

Kobbe

Nicolae

et al. 2004

Molecular and Cellular Biology

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Matrilin-3 belongs to the matrilin family of extracellular matrix (ECM) proteins and is primarily expressed in cartilage. Mutations in the gene encoding human matrilin-3 (MATN-3) lead to autosomal dominant skeletal disorders, such as multiple epiphyseal dysplasia (MED), which is characterized by short stature and earlyonset osteoarthritis, and bilateral hereditary microepiphyseal dysplasia, a variant form of MED characterized by pain in the hip and knee joints. To assess the function of matrilin-3 during skeletal development, we have generated Matn-3 null mice. Homozygous mutant mice appear normal, are fertile, and show no obvious skeletal malformations. Histological and ultrastructural analyses reveal endochondral bone formation indistinguishable from that of wild-type animals. Northern blot, immunohistochemical, and biochemical analyses indicated no compensatory upregulation of any other member of the matrilin family. Altogether, our findings suggest functional redundancy among matrilins and demonstrate that the phenotypes of MED disorders are not caused by the absence of matrilin-3 in cartilage ECM.

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“…2 Via this coiled coil domain, matrilin-3 is able to form homotetramers as well as heterotrimers and -tetramers with matrilin-1. [3][4][5] In addition to hetero-oligomeric assembly with certain other family members, all matrilins have been shown to interact with a variety of both collagenous and non-collagenous proteins, suggesting a function as adaptor proteins within the ECM. [6][7][8][9][10] Moreover, the formation of filamentous structures in the pericellular matrix of cultured cells has been described for all four matrilins.…”

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confidence: 99%