similar problems and require chaperone protection in the membrane. Amazing teamwork @Stanford Congratulations to all authors with and without bluesky accounts @meghaag.bsky.social @caseygifford.bsky.social @algao.bsky.social @bhartisingal.bsky.social

We found that EMC engages the Ca2+ channel co-translationally as part of a large ribosome-multipass-translocon-EMC supercomplex, likely to protect vulnerable channel folding intermediates from misrecognition by ER quality control. We anticipate that other multi-bundle channels/transporters face

We solved the cryo-EM structure of an inhibitory Nb bound to the EMC showing a steric clash with Ca2+ channel binding. When introduced into cardiomyocytes that endogenously express both EMC and Ca2+ channel, this Nb strongly blocked contraction (no beating or calcium waves)

it remained unclear if EMC's well-studied insertase activity or a potentially novel chaperone function is required. We established function-separating mutations and selective nanobody inhibitors to demonstrate that Ca2+ channels are degraded when EMC's chaperone function is specifically perturbed.

Voltage-gated calcium channels are the key drivers of heart muscle contraction (see green oscillating calcium waves in the video above). They are first inserted into the lipid bilayer, folded and assembled at the ER membrane by ER biogenesis factors. The EMC was speculated to be involved but ...