title: HCF-1 is cleaved in the active site of O-GlcNAc transferase.
abstract: Host cell factor-1 (HCF-1), a transcriptional co-regulator of human cell-cycle progression, undergoes proteolytic maturation in which any of six repeated sequences is cleaved by the nutrient-responsive glycosyltransferase, O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). We report that the tetratricopeptide-repeat domain of O-GlcNAc transferase binds the carboxyl-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site above uridine diphosphate-GlcNAc. The conformation is similar to that of a glycosylation-competent peptide substrate. Cleavage occurs between cysteine and glutamate residues and results in a pyroglutamate product. Conversion of the cleavage site glutamate into serine converts an HCF-1 proteolytic repeat into a glycosylation substrate. Thus, protein glycosylation and HCF-1 cleavage occur in the same active site.
authors: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors: Michael B
authors: MB
authors: Lazarus
authors: Jiaoyang
authors: J
authors: Jiang
authors: Vaibhav
authors: V
authors: Kapuria
authors: Tanja
authors: T
authors: Bhuiyan
authors: John
authors: J
authors: Janetzko
authors: Wesley F
authors: WF
authors: Zandberg
authors: David J
authors: DJ
authors: Vocadlo
authors: Winship
authors: W
authors: Herr
authors: Suzanne
authors: S
authors: Walker
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006031:Glycosylation; D051863:Host Cell Factor C1 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000737:chemistry / Q000378:metabolism
chemical_list: C497692:HCFC1 protein, human; D051863:Host Cell Factor C1; D011993:Recombinant Fusion Proteins; D014537:Uridine Diphosphate N-Acetylglucosamine; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D011761:Pyrrolidonecarboxylic Acid