Heat-shocked calreticulin (HS-CRT) is better able to prevent protein aggregation (purple bars).


Achaperone is supposed to keep its cool when temperatures get hot. But Syed Rizvi, Laura Mancino, Malini Raghavan (University of Michigan, Ann Arbor, MI), and colleagues show that calreticulin—a glycoprotein chaperone—starts to melt in the heat. The resulting structural changes actually improve its chaperone activity and may also occur transiently under normal conditions.

Calreticulin is a stress-induced chaperone that helps glycoproteins such as MHC Class I molecules fold properly in the ER by binding to the target proteins' sugar groups. The new results show that at high temperatures or low calcium levels, calreticulin can also bind independently of sugars and thus more effectively inhibit protein aggregation.

Protein binding was accompanied by structural changes in calreticulin, including oligomerization at high temperatures. “It has remarkable conformational lability for a chaperone,” says Raghavan. “Its stability is like [that of] the substrates themselves.” The COOH-terminal tail was found to be necessary to inhibit the oligomerized form, but its effect may be overcome at high temperature or low calcium so that the protein can help out when the ER is overwhelmed.


Rizvi, S.M., et al.
Mol. Cell.