6r6p

Structure of XBP1u-paused ribosome nascent chain complex (rotated state)

Loading... Status: waiting for Mol* initialization Structural highlights 6r6p is a 10 chain structure with sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Ligands: MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G1TT27_RABIT Publication Abstract from PubMed XBP1u, a central component of the unfolded protein response (UPR), is a mammalian protein containing a functionally critical translational arrest peptide (AP). Here, we present a 3 A cryo-EM structure of the stalled human XBP1u AP. It forms a unique turn in the ribosomal exit tunnel proximal to the peptidyl transferase center where it causes a subtle distortion, thereby explaining the temporary translational arrest induced by XBP1u. During ribosomal pausing the hydrophobic region 2 (HR2) of XBP1u is recognized by SRP, but fails to efficiently gate the Sec61 translocon. An exhaustive mutagenesis scan of the XBP1u AP revealed that only 8 out of 20 mutagenized positions are optimal; in the remaining 12 positions, we identify 55 different mutations increase the level of translational arrest. Thus, the wildtype XBP1u AP induces only an intermediate level of translational arrest, allowing efficient targeting by SRP without activating the Sec61 channel. Structural and mutational analysis of the ribosome-arresting human XBP1u.,Shanmuganathan V, Schiller N, Magoulopoulou A, Cheng J, Braunger K, Cymer F, Berninghausen O, Beatrix B, Kohno K, Heijne GV, Beckmann R Elife. 2019 Jun 27;8. pii: 46267. doi: 10.7554/eLife.46267. PMID:31246176 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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