9ZZ6

The ER membrane protein complex acts as a chaperone to promote voltage-gated calcium channel assembly

Summary for 9ZZ6

• Entry DOI: 10.2210/pdb9zz6/pdb
• EMDB information: 74981
• Descriptor: ER membrane protein complex subunit 1, Nanobody G9, Nanobody E2, ... (13 entities in total)
• Functional Keywords: protein biogenesis, endoplasmic reticulum, er, chaperone, insertase, complex, membrane protein, chaperone-immune system complex, chaperone/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 11
• Total formula weight: 333275.29

Authors

Singal, B.,Biswal, M.,Pleiner, T. (deposition date: 2026-01-06, release date: 2026-02-18)

Primary citation

Stanton, M.,Singal, B.,Biswal, M.,Agarwal, M.,Scheuing, C.E.,Vargas, G.D.,Gao, A.,Gifford, C.A.,Pleiner, T.
The ER membrane protein complex acts as a chaperone to promote the biogenesis of multi-bundle membrane proteins.
Biorxiv, 2026

PubMed Abstract: Nearly half of the ~5,000 human membrane proteins need to assemble into stoichiometric complexes as part of their biogenesis at the endoplasmic reticulum (ER) membrane. How ER resident biogenesis factors coordinate membrane insertion, folding and assembly is not well understood. Here, we demonstrate that the ER membrane protein complex (EMC) insertase additionally acts as a chaperone to facilitate the assembly of heterotrimeric voltage-gated calcium channels (Ca). Using function-separating mutations and inhibitory nanobodies we show that nascent Ca channels are degraded prematurely when EMC's chaperone function is selectively perturbed. Blocking EMC's chaperone function strongly impaired Ca-dependent cardiomyocyte contraction. EMC engagement of the pore-forming Caα-subunit occurred co-translationally and required Caα's first transmembrane domain bundle to protrude from the nascent ribosome•Sec61•multipass translocon complex. Our findings establish a chaperone function for the EMC and reveal that biogenesis of multi-bundle membrane proteins requires a highly orchestrated, co-translational interplay between ER biogenesis factors.

PubMed: 41648177
DOI: 10.64898/2026.01.14.699575

Experimental method

ELECTRON MICROSCOPY (4.16 Å)