tailieunhanh - Báo cáo khoa học: Paralog of the formylglycine-generating enzyme – retention in the endoplasmic reticulum by canonical and noncanonical signals

Formylglycine-generating enzyme (FGE) catalyzes in newly synthesized sul-fatases the oxidation of a specific cysteine residue to formylglycine, which is the catalytic residue required for sulfate ester hydrolysis. This post-trans-lational modification occurs in the endoplasmic reticulum (ER), and is an essential step in the biogenesis of this enzyme family. | ễFEBS Journal Paralog of the formylglycine-generating enzyme -retention in the endoplasmic reticulum by canonical and noncanonical signals Santosh Lakshmi Gande1 Malaiyalam Mariappan1 Bernhard Schmidt1 Thomas H. Pringle2 Kurt von Figura1 and Thomas Dierks3 1 Zentrum fur Biochemie und Molekulare Zellbiologie Abteilung Biochemie II Universitat Gottingen Germany 2 Sperling Foundation Eugene OR USA 3 Fakultat fur Chemie Biochemie I Universitat Bielefeld Germany Keywords endoplasmic reticulum formylglycine-generating enzyme KDEL receptor protein retention SUMF2 Correspondence T. Dierks Fakultat fur Chemie Biochemie I Universitat Bielefeld Universitatsstr. 25 33615 Bielefeld Germany Fax 49 521 106 6014 Tel 49 521 106 2092 E-mail Website http chemie bc1 Received 28 October 2007 revised 17 December 2007 accepted 4 January 2008 doi Formylglycine-generating enzyme FGE catalyzes in newly synthesized sulfatases the oxidation of a specific cysteine residue to formylglycine which is the catalytic residue required for sulfate ester hydrolysis. This post-translational modification occurs in the endoplasmic reticulum ER and is an essential step in the biogenesis of this enzyme family. A paralog of FGE pFGE also localizes to the ER. It shares many properties with FGE but lacks formylglycine-generating activity. There is evidence that FGE and pFGE act in concert possibly by forming complexes with sulfatases and one another. Here we show that human pFGE but not FGE is retained in the ER through its C-terminal tetrapeptide PGEL a noncanonical variant of the classic KDEL ER-retention signal. Surprisingly PGEL although having two nonconsensus residues PG confers efficient ER retention when fused to a secretory protein. Inducible coexpression of pFGE at different levels in FGE-expressing cells did not significantly influence the kinetics of FGE secretion suggesting that pFGE is not a retention .