Collagens and collagen-related diseases

Abstract

The collagen superfamily of proteins plays a dominant role in maintaining the integrity of various tissues and also has a number of other important functions. The superfamily now includes more than 20 collagen types with altogether at least 38 distinct polypeptide chains, and more than 15 additional proteins that have collagen-like domains. Most collagens form polymeric assemblies, such as fibrils, networks and filaments, and the superfamily can be divided into several families based on these assemblies and other features. All collagens also contain noncollagenous domains, and many of these have important functions that are distinct from those of the collagen domains. Major interest has been focused on endostatin, a fragment released from type XVIII collagen, which potently inhibits angiogenesis and tumour growth. Collagen synthesis requires eight specific post-translational enzymes, some of which are attractive targets for the development of drugs to inhibit collagen accumulation in fibrotic diseases. The critical roles of collagens have been clearly illustrated by the wide spectrum of diseases caused by the more than 1,000 mutations that have thus far been identified in 22 genes for 12 out of the more than 20 collagen types. These diseases include osteogenesis imperfecta, many chondrodysplasias, several subtypes of the Ehlers-Danlos syndrome, Alport syndrome, Bethlem myopathy, certain subtypes of epidermolysis bullosa, Knobloch syndrome and also some cases of osteoporosis, arterial aneurysms, osteoarthrosis, and intervertebral disc disease. The characterization of mutations in additional collagen genes will probably add further diseases to this list. Mice with genetically engineered collagen mutations have proved valuable for defining the functions of various collagens and for studying many aspects of the related diseases.

Chronic tendon pathology: molecular basis and therapeutic implications

“…They all possess a small protein core (36)(37)(38)(39)(40)(41)(42) The most abundant proteoglycan in tendon is decorin, although biglycan is also present in small amounts (Ref. 57).…”

The bone morphogenetic protein 1/Tolloid-like metalloproteinases

“…1). Cleavage of both N-and C-propeptides occurs via highly specific calciumdependent metalloproteinases with neutral pH optima (Hojima et al, 1985;Kessler et al, 1986), and is necessary for releasing the mature triple helical portion of the molecule for proper self-assembly into fibrils (Myllyharju and Kivirikko, 2001;Canty and Kadler, 2005) Disintegrin And Metalloproteinase with ThromboSpondin repeats) family (Greenspan and Wang, 2005); specifically via the structurally similar proteinases ADAMTS2, 3 and 14, which have overlapping but differing distributions in tissues (Colige et al, 1997;Le Goff et al, 2006;Wang et al, 2003). Deficiencies in N-propeptide processing leads to the arthrochalasis and dermatosparaxis forms of Ehlers-Danlos Syndrome (EDS) (Byers, 1995).…”

4‐Chloroprolines: Synthesis, conformational analysis, and effect on the collagen triple helix

“…1 The three-dimensional structure of collagen was determined in the 1950s2 -6 to be a right-handed triple helix formed by the parallel coiling of three left-handed polyproline II-type (PPII) strands about a common axis. At least 28 different members of the collagen superfamily of proteins have been discovered to date, as well as a number of other proteins with triple-helical, collagenous domains.…”