The architecture of EMC reveals a path for membrane protein insertion.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
A visual intracellular classification strategy for uncharacterized human proteins.
Towards a proteome-scale map of the human protein-protein interaction network.
Defining human ERAD networks through an integrative mapping strategy.
A proteome-scale map of the human interactome network.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
Architecture of the human interactome defines protein communities and disease networks.
The ER membrane protein complex is a transmembrane domain insertase.
The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins.
Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
EMC Is Required to Initiate Accurate Membrane Protein Topogenesis.
A reference map of the human binary protein interactome.
Structural basis for membrane insertion by the human ER membrane protein complex.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
WNK1 is an assembly factor for the human ER membrane protein complex.
-
EMC2 is the superhelical architectural scaffold of the EMC, organized around the soluble EMC2-EMC8/9 heterodimer and anchoring both cytosolic and membrane-spanning subunits.
-
WNK1 uses a conserved amphipathic helix to stabilize soluble EMC2 by binding the EMC2-EMC8 interface, preventing its ubiquitination and permitting EMC assembly.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Multimodal cell maps as a foundation for structural and functional genomics.
UniProt entry Q15006 (EMC2_HUMAN), ER membrane protein complex subunit 2
A selectivity filter in the ER membrane protein complex limits protein misinsertion at the ER.
-
The EMC inserts tail-anchored substrates via a hydrophilic vestibule whose positively charged entrance acts as a charge-repulsion selectivity filter; deletion of the EMC4 cytosolic EMC2-binding site impairs biogenesis of a canonical EMC-dependent tail-anchored client (SQS/FDFT1), underscoring the functional importance of EMC2-mediated cytosolic assembly interfaces.
EMC rectifies the topology of multipass membrane proteins.
-
The EMC mediates post-translational insertion of C-terminal transmembrane domains of multipass membrane proteins (e.g. SOAT1) to rectify their topology after ribosome release; this sequential co-/post-translational mechanism may apply to ~250 diverse multipass proteins, expanding the EMC client scope.
The EMC acts as a chaperone for membrane proteins.
-
Beyond its insertase activity, the EMC has a chaperone mode that engages client transmembrane domains (via the EMC1 subunit) and modulates their orientation in the lipid bilayer; the authors build a machine-learning client predictor, establishing the EMC as a multifunctional membrane-protein biogenesis machine.