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.