Search Results: Unfolded protein response

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Figure 1.Protein folding and quality control in the endoplasmic reticulum (ER). (Left) A polypeptide synthesized on a ribosome bound to the ER membrane is translocated during the course of chain elongation (that is, cotranslationally) into the lumen of the ER. A nonglycosylated released unfolded polypeptide or nonglycosylated regions of a nascent glycoprotein bearing exposed hydrophobic polypeptide regions, which in a fully folded protein are buried in the interior of the protein, bind to BiP carrying ADP (adenosine diphosphate), preventing them from aggregating with other unfolded proteins. An enzyme, called an exchange factor, exchanges the ADP for ATP (adenosine triphosphate) on the bound BiP, which leads to release of BiP from the unfolded protein. While the protein is not bound to BiP, it has a chance to continue on its folding pathway. At the same time, BiP hydrolyzes the bound ATP to yield BiP-ADP and inorganic phosphate [HPO42-; abbreviated Pi]. Cycles of BiP binding, ATP for ADP exchange, BiP release, and ATP hydrolysis repeat until the protein is folded and no longer binds to BiP. During ER stress, the amount of unfolded proteins in the ER lumen exceeds the amount of BiP that can handle them, a condition resulting in activation of the UPR. (Right) After release of a partially folded protein from BiP, the protein is bound by the chaperone GRP94 and the lectin chaperones, calnexin (CNX) and calreticulin (CRT). CNX and CRT bind to oligosaccharides attached to the protein. They are released from glycoproteins upon enzymatic removal of a glucose moiety. Readdition of this glucose moiety to unfolded glycoproteins triggers a second round of interaction with the lectin chaperones. These cycles of glucose removal and addition continue until folding of the glycoprotein is complete. Glycoproteins that take a long time to fold and are intermittently bound to the lectin chaperones over long time periods are delivered to a channel in the ER membrane, possibly the SEC61 channel, where they are translocated to the cytosol for degradation in the proteasome.

From Encyclopedia article 'Unfolded protein response'

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Figure 1.Protein folding and quality control in the ER. (Left) A polypeptide synthesized on a ribosome bound to the ER membrane is translocated during the course of chain elongation (that is, cotranslationally) into the lumen of the ER. A nonglycosylated released unfolded polypeptide or nonglycosylated regions of a nascent glycoprotein bearing exposed hydrophobic polypeptide regions, which in a fully folded protein are buried in the interior of the protein, bind to BiP carrying ADP (adenosine diphosphate), preventing it from aggregating with other unfolded proteins. An enzyme, called an exchange factor, exchanges the ADP for ATP (adenosine triphosphate) on the bound BiP, which leads to release of BiP from the unfolded protein. While the protein is not bound to BiP, it has a chance to continue on its folding pathway. At the same time, BiP hydrolyzes the bound ATP to yield BiP-ADP and inorganic phosphate [HPO42-; abbreviated Pi]. Cycles of BiP binding, ATP for ADP exchange, BiP release, and ATP hydrolysis repeat until the protein is folded and no longer binds to BiP. During ER stress, the amount of unfolded proteins in the ER lumen exceed the amount of BiP that can handle them, a condition resulting in activation of the UPR. (Right) After release of a partially folded protein from BiP, the protein is bound by the chaperone GRP94 and the lectin chaperones CNX and CRT. CNX and CRT bind to oligosaccharides attached to the protein. They are released from glycoproteins upon enzymatic removal of a glucose moiety. Readdition of this glucose moiety to unfolded glycoproteins triggers a second round of interaction with the lectin chaperones. These cycles of glucose removal and addition continue until folding of the glycoprotein is complete. Glycoproteins that take a long time to fold and are intermittently bound to the lectin chaperones over long time periods are delivered to a channel in the ER membrane, possibly the SEC61 channel, where they are translocated to the cytosol for degradation in the proteasome.

From update 'Unfolded protein response'

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Figure 2.Principal signaling pathways in the human unfolded protein response (UPR). (Reprinted from Current Molecular Medicine, copyright © 2006, with permission from Bentham Science Publishers)

From Encyclopedia article 'Unfolded protein response'