The Different Roles of Aggrecan Interaction Domains |
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Authors: | Anders Aspberg |
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Institution: | Department of Biology, Copenhagen University, Copenhagen N, Denmark |
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Abstract: | The aggregating proteoglycans of the lectican family are important components of
extracellular matrices. Aggrecan is the most well studied of these and is central to
cartilage biomechanical properties and skeletal development. Key to its biological
function is the fixed charge of the many glycosaminoglycan chains, that provide the basis
for the viscoelastic properties necessary for load distribution over the articular
surface. This review is focused on the globular domains of aggrecan and their role in
anchoring the proteoglycans to other extracellular matrix components. The N-terminal G1
domain is vital in that it binds the proteoglycan to hyaluronan in ternary complex with
link protein, retaining the proteoglycan in the tissue. The importance of the C-terminal
G3 domain interactions has recently been emphasized by two different human hereditary
disorders: autosomal recessive aggrecan-type spondyloepimetaphyseal dysplasia and
autosomal dominant familial osteochondritis dissecans. In these two conditions, different
missense mutations in the aggrecan C-type lectin repeat have been described. The resulting
amino acid replacements affect the ligand interactions of the G3 domain, albeit with
widely different phenotypic outcomes. |
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Keywords: | extracellular matrix cartilage aggrecan protein interactions chondrodysplasia osteochondritis dissecans |
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