We made nanobodies that make your heart🫀 stop 🛑beating. Keep reading to learn how this taught us about how large membrane proteins like ion channels are folded and assembled in human cells. Beyond excited to share my lab's first preprint: Please 🔄 bit.ly/49A0PtD
The ER membrane protein complex acts as a chaperone to promote the biogenesis of multi-bundle membrane proteins https://www.biorxiv.org/content/10.64898/2026.01.14.699575v1
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 ...
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
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.
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)
How do mitochondrial ribosomes keep pace with membrane insertion?
Now out in NSMB: We show that mitoribosomes slow down at defined positions linked to membrane insertion and protein topology: rdcu.be/fhqIT
#Mitochondria #Ribosome #CryoEM
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
2025 Basic Award winner Dirk Görlich @mpsgoettingen.bsky.social advises scientists to overcome "headwinds against new ways of thinking" by putting ideas to the "strictest possible test" and finding satisfaction in the journey, not just the destination. #LaskerAwards
✨Excited that the main project of my PhD is now available as a pre-print on #bioRxiv
Here, we used #CryoET to visualise mitochondrial proteostatic stress and together with SPA #CryoEM shed light into the functional cycle of the Hsp60:10 chaperone system. #TeamTomo
🔗 www.biorxiv.org/content/10.1...
Video
Nature Structural & Molecular Biology - Schöndorf and Petrychenko et al. show that mitochondrial translation speed is coupled to OXA1L-mediated inner membrane insertion, with...