title: Mimivirus collagen is modified by bifunctional lysyl hydroxylase and glycosyltransferase enzyme.
abstract: Collagens, the most abundant proteins in animals, are modified by hydroxylation of proline and lysine residues and by glycosylation of hydroxylysine. Dedicated prolyl hydroxylase, lysyl hydroxylase, and collagen glycosyltransferase enzymes localized in the endoplasmic reticulum mediate these modifications prior to the formation of the collagen triple helix. Whereas collagen-like proteins have been described in some fungi, bacteria, and viruses, the post-translational machinery modifying collagens has never been described outside of animals. We demonstrate that the L230 open reading frame of the giant virus Acanthamoeba polyphaga mimivirus encodes an enzyme that has distinct lysyl hydroxylase and collagen glycosyltransferase domains. We show that mimivirus L230 is capable of hydroxylating lysine and glycosylating the resulting hydroxylysine residues in a native mimivirus collagen acceptor substrate. Whereas in animals from sponges to humans the transfer of galactose to hydroxylysine in collagen is conserved, the mimivirus L230 enzyme transfers glucose to hydroxylysine, thereby defining a novel type of collagen glycosylation in nature. The presence of hydroxylysine in mimivirus proteins was confirmed by amino acid analysis of mimivirus recovered from A. polyphaga cultures. This work shows for the first time that collagen post-translational modifications are not confined to the domains of life. The utilization of glucose instead of the galactose found throughout animals as well as a bifunctional enzyme rather than two separate enzymes may represent a parallel evolutionary track in collagen biology. These results suggest that giant viruses may have contributed to the evolution of collagen biology.
authors: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Kelvin B
authors: KB
authors: Luther
authors: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Andreas J
authors: AJ
authors: Hülsmeier
authors: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Belinda
authors: B
authors: Schegg
authors: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors: Stefan A
authors: SA
authors: Deuber
authors: Unité de Recherche sur les Maladies Infectieuses et Tropicales Émergentes, CNRS Unité Mixte de Recherche Institut de Recherche pour le Développement 6236, Faculté de Médecine, Université de la Méditerranée, 13385 Marseille cedex 5, France.
authors: Didier
authors: D
authors: Raoult
authors: Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Electronic address: thennet@access.uzh.ch.
authors: Thierry
authors: T
authors: Hennet
mesh_terms: D000048:Acanthamoeba / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000378:metabolism; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D005822:Genetic Vectors; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry*; D006801:Humans; D006901:Hydroxylysine / Q000737:chemistry; D056686:Mimiviridae / Q000378:metabolism*; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D006901:Hydroxylysine; D003094:Collagen; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D016695:Glycosyltransferases