Calnexin, calreticulin, and ERp57: teammates in glycoprotein folding.
In eukaryotic cells, the endoplasmic reticulum (ER) plays an essential role in the synthesis and maturation of a variety of important secretory and membrane proteins. For glycoproteins, the ER possesses a dedicated maturation system, which assists folding and ensures the quality of final products before ER release. Essential components of this system include the lectin chaperones calnexin (CNX) and calreticulin (CRT) and their associated co-chaperone ERp57, a glycoprotein specific thiol-disulfide oxidoreductase. The significance of this system is underscored by the fact that CNX and CRT interact with practically all glycoproteins investigated to date, and by the debilitating phenotypes revealed in knockout mice deficient in either gene. Compared to other important chaperone systems, such as the Hsp70s, Hsp90s and GroEL/GroES, the principles whereby this system works at the molecular level are relatively poorly understood. However, recent structural and biochemical data have provided important new insights into this chaperone system and present a solid basis for further mechanistic studies.
Ellgaard
Lars
L
Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
Frickel
Eva-Maria
EM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D037281:Calnexin / Q000378:metabolism*; D037282:Calreticulin / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007535:Isomerases / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism
D037282:Calreticulin; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D037281:Calnexin; D000255:Adenosine Triphosphate; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D002118:Calcium