br Atypical collagen glycosylation The

Atypical collagen glycosylation The disaccharide Glc(α1-2)Gal(β1-O) decorating collagens is strongly conserved across the animal kingdom, yet for every rule, nature provides exceptions. The deep-sea worm Riftia pachyptila of the phylum Annelida represents an intriguing exception. R. pachyptila is protected by a thick Budesonide mainly consisting of fibrillar collagen. This collagen contains only little of 4-hydroxyproline, but large amounts of galactosylated threonine []. Structural analysis of R. pachyptila collagen revealed that galactosylated threonine indeed replaces hydroxyproline at the Yaa position of the collagen motif [45]. Galactosylated threonine was shown to contribute to the formation of stable triple helical collagen at temperatures up to 37°C, which prevail by the hydrothermal vents where R. pachyptila dwells. Collagen glycosylation also occurs outside of animals. For example, in prokaryotes, collagen-like proteins have been described in several pathogenic Streptococci such as Streptococcus pyogenes and Streptococcus pneumoniae [46]. The cyanobacterium Trichodesmium erythraeum also expresses TrpA [47], a large collagen protein involved in cell–cell adhesion, which enables the formation of filamentous colonies of up to 1 cm in length. Collagens also appear in viruses, such as the giant viruses of the family of Mimiviridae [48]. The genome of the prototype Mimivirus comprises seven collagen genes as well as genes encoding glycosyltransferases involved in the glycosylation of Hyl in collagen [49]. Glycosylation of Mimivirus collagen is initiated by a bifunctional enzyme that catalyzes the hydroxylation of lysine and the transfer of Glc to Hyl []. Taking in account the broad occurrence of collagen-like proteins across the domains of life and in viruses, further forms of collagen glycosylation are likely to be unraveled over the next years.
Conclusion
Conflict of interest statement
References and recommended reading Papers of particular interest, published within the period of review, have been highlighted as:
Acknowledgement This work was supported by the Swiss National Science Foundation grant 310030_149949.
Introduction Prolyl 4-hydroxylases (P4Hs) belong to the family of Fe2+ and 2-oxoglutarate- dependent oxygenases that catalyze the post-translational hydroxylation of proline in peptide linkages and require Fe2+, 2-oxoglutarate, O2, and ascorbate [1,2]. In animals, collagen P4Hs act on prolines present in collagen and collagen-like proteins, that is essential for stabilizing the collagen triple-helical structure. PHDs are another type of P4Hs, function as oxygen sensors since they mediate oxygenases catalyze reactions but have a high K for oxygen as a substrate [3,4]. Under normoxia, PHD2 modifies the HIF1α (hypoxia-inducible transcription factor) and triggers its ubiquitination and subsequent degradation. Under hypoxia, HIF1α cannot be modified by PHD2, and under these conditions, it is translocated into the nucleus, where it activates the expression of a series of genes [5,6]. In plants, P4Hs catalyze the hydroxylation of proline residues in hydroxyproline (Hyp)-rich glycoprotein (HRGPs), the major structural components of plant and green algae cell walls [7,8]. AtP4Hs genes have different expression patterns in response to hypoxia in Arabidopsis thaliana, suggesting they also function as hypoxia-sensing proteins [[9], [10], [11]]. The presence of HIF1α-PHDs homologs in bacteria and other eukaryotes reveals that this oxygen sensing systems may have very ancient origins [12,13]. Crystallographic studies of several P4Hs reveal that the catalytic sites are located at a center double-strand β-helix (DSBH) fold, the highly conserved HX(D/E) … H motif for Fe2+coordination and the C-5 carboxylate of 2-oxoglutarate binds to a basic lysyl or arginyl residues [14]. Prokaryotic and eukaryotic P4Hs structural information have provided insights into the properties and substrate selectivity of different P4Hs, which may aid in the development of selective inhibitors of these protein modification enzymes.