Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins

Olivari, Silvia; Molinari, Maurizio

doi:10.1016/j.febslet.2007.04.070

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Volume 581, Issue 19 , Pages 3658-3664, 31 July 2007

Glycoprotein folding and the role of EDEM1, EDEM2 and EDEM3 in degradation of folding-defective glycoproteins

Edited by Roberto Sitia

Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland

Received 2 March 2007; accepted 19 April 2007. published online 03 May 2007.

Abstract

Proteins synthesized in the endoplasmic reticulum (ER) lumen are exposed to several dedicated chaperones and folding factors that ensure efficient maturation. Nevertheless, protein folding remains error-prone and mutations in the polypeptide sequence may significantly reduce folding-efficiency. Folding-incompetent proteins carrying N-glycans are extracted from futile folding cycles in the calnexin chaperone system upon intervention of EDEM1, EDEM2 and EDEM3, three ER-stress-induced members of the glycosyl hydrolase 47 family. This review describes current knowledge about mechanisms regulating folding and disposal of glycoproteins.

Keywords: Endoplasmic reticulum, Protein folding, ER-associated degradation (ERAD), EDEM1, EDEM2, EDEM3