Conversion of cysteine to formylglycine: a protein modification in the endoplasmic reticulum.
In sulfatases a Calpha-formylglycine residue is found at a position where their cDNA sequences predict a cysteine residue. In multiple sulfatase deficiency, an inherited lysosomal storage disorder, catalytically inactive sulfatases are synthesized which retain the cysteine residue, indicating that the Calpha-formylglycine residue is required for sulfatase activity. Using in vitro translation in the absence or presence of transport competent microsomes we found that newly synthesized sulfatase polypeptides carry a cysteine residue and that the oxidation of its thiol group to an aldehyde is catalyzed in the endoplasmic reticulum. A linear sequence of 16 residues surrounding the Cys-69 in arylsulfatase A is sufficient to direct the oxidation. This novel protein modification occurs after or at a late stage of cotranslational protein translocation into the endoplasmic reticulum when the polypeptide is not yet folded to its native structure.
Dierks
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T
Institut für Biochemie und Molekulare Zellbiologie, Abteilung Biochemie II, Universität Göttingen, Gosslerstrasse 12d, 37073 Göttingen, Germany.
Schmidt
B
B
von Figura
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K
D000409:Alanine / Q000031:analogs & derivatives* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D001692:Biological Transport; D002553:Cerebroside-Sulfatase / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000201:enzymology; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational
C524739:C(alpha)-formylglycine; D002553:Cerebroside-Sulfatase; D003545:Cysteine; D000409:Alanine; D005998:Glycine