6r5q
Structure of XBP1u-paused ribosome nascent chain complex (post-state)
Structural highlights
FunctionRS11_RABIT Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit (PubMed:23873042, PubMed:25601755, PubMed:26245381, PubMed:27863242, PubMed:30517857). During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity).[UniProtKB:P62280][1] [2] [3] [4] [5] Publication Abstract from PubMedXBP1u, 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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