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cryo-EM structure of human EMC
Structural highlights
DiseaseEMC1_HUMAN Global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionPublication Abstract from PubMedThe endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in stabilizing and trafficking membrane proteins. However, the structural basis and regulation of its multifunctionality remain elusive. Here, we report cryo-electron microscopy structures of human EMC in apo- and voltage-dependent anion channel (VDAC)-bound states at resolutions of 3.47 A and 3.32 A, respectively. We discovered a specific interaction between VDAC proteins and the EMC at mitochondria-ER contact sites, which is conserved from yeast to humans. Moreover, we identified a gating plug located inside the EMC hydrophilic vestibule, the substrate-binding pocket for client insertion. Conformation changes of this gating plug during the apo-to-VDAC-bound transition reveal that the EMC unlikely acts as an insertase in the VDAC1-bound state. Based on the data analysis, the gating plug may regulate EMC functions by modifying the hydrophilic vestibule in different states. Our discovery offers valuable insights into the structural basis of EMC's multifunctionality. Structural insights into human EMC and its interaction with VDAC.,Li M, Zhang C, Xu Y, Li S, Huang C, Wu J, Lei M Aging (Albany NY). 2024 Mar 15;16(6):5501-5525. doi: 10.18632/aging.205660. Epub , 2024 Mar 15. PMID:38517390[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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