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Calnexin chaperone interaction with glycoproteins is well established, whereas non-glycoprotein interaction is still under debate. These authors show that calnexin can sense improper folding or assembly of a non-glycosylated protein via its transmembrane domain. RNAi convincingly shows that calnexin only retards mutant protein degradation, suggesting an active role for calnexin in intramembrane QC.
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Swanton E., High S., Woodman P. Role of calnexin in the glycan-independent quality control of proteolipid protein. EMBO J. 22:2003;2948-2958 Calnexin chaperone interaction with glycoproteins is well established, whereas non-glycoprotein interaction is still under debate. These authors show that calnexin can sense improper folding or assembly of a non-glycosylated protein via its transmembrane domain. RNAi convincingly shows that calnexin only retards mutant protein degradation, suggesting an active role for calnexin in intramembrane QC.
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In a back-to-back publication with Molinari and colleagues, these two teams of authors show for the first time that mannose-binding protein EDEM accepts terminally misfolded glycoproteins directly from calnexin. Clearly, EDEM is the link for calnexin to ERAD. Also, next to ERp57, EDEM is the second protein known to directly interact with calnexin to perform QC.
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Oda Y., Hosokawa N., Wada I., Nagata K. EDEM as an acceptor of terminally misfolded glycoproteins released from calnexin. Science. 299:2003;1394-1397 In a back-to-back publication with Molinari and colleagues, these two teams of authors show for the first time that mannose-binding protein EDEM accepts terminally misfolded glycoproteins directly from calnexin. Clearly, EDEM is the link for calnexin to ERAD. Also, next to ERp57, EDEM is the second protein known to directly interact with calnexin to perform QC.
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FRET showed that a nascent transmembrane segment of a membrane protein folds in a compact, probably helical, conformation inside the ribosomal tunnel, in contrast to a nascent secretory protein. The ribosomal protein L17 that extends from near the ribosomal exit site to the inside of the tunnel specifically interacts with the transmembrane segment. L17 may signal to the translocon pore that a transmembrane segment is arriving, which needs to be inserted into the ER membrane.
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