6so5

Homo sapiens WRB/CAML heterotetramer in complex with a TRC40 dimerHomo sapiens WRB/CAML heterotetramer in complex with a TRC40 dimer

Structural highlights 6so5 is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 6so6 Gene: ASNA1, ARSA, TRC40 (HUMAN), WRB, CHD5 (HUMAN), CAMLG, CAML (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CAMLG_HUMAN] Likely involved in the mobilization of calcium as a result of the TCR/CD3 complex interaction. Binds to cyclophilin B. [GET1_HUMAN] Receptor for GET3/TRC40-mediated insertion of tail-anchored (TA) proteins into the ER membrane. Publication Abstract from PubMed Membrane protein biogenesis faces the challenge of chaperoning hydrophobic transmembrane helices for faithful membrane insertion. The guided entry of tail-anchored proteins (GET) pathway targets and inserts tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane with an insertase (yeast Get1/Get2 or mammalian WRB/CAML) that captures the TA from a cytoplasmic chaperone (Get3 or TRC40, respectively). Here, we present cryo-electron microscopy reconstructions, native mass spectrometry, and structure-based mutagenesis of human WRB/CAML/TRC40 and yeast Get1/Get2/Get3 complexes. Get3 binding to the membrane insertase supports heterotetramer formation, and phosphatidylinositol binding at the heterotetramer interface stabilizes the insertase for efficient TA insertion in vivo. We identify a Get2/CAML cytoplasmic helix that forms a "gating" interaction with Get3/TRC40 important for TA insertion. Structural homology with YidC and the ER membrane protein complex (EMC) implicates an evolutionarily conserved insertion mechanism for divergent substrates utilizing a hydrophilic groove. Thus, we provide a detailed structural and mechanistic framework to understand TA membrane insertion. Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.,McDowell MA, Heimes M, Fiorentino F, Mehmood S, Farkas A, Coy-Vergara J, Wu D, Bolla JR, Schmid V, Heinze R, Wild K, Flemming D, Pfeffer S, Schwappach B, Robinson CV, Sinning I Mol Cell. 2020 Oct 1;80(1):72-86.e7. doi: 10.1016/j.molcel.2020.08.012. Epub 2020, Sep 9. PMID:32910895 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 6so5, resolution 4.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image