Evidence map›Paper›PMID 31246176›Full record

ArticleeLife2019

Structural and mutational analysis of the ribosome-arresting human XBP1u.

Vivekanandan Shanmuganathan, Nina Schiller, Anastasia Magoulopoulou, Jingdong Cheng, Katharina Braunger, Florian Cymer, Otto Berninghausen, Birgitta Beatrix, Kenji Kohno, Gunnar von Heijne and 1 more

Abstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

59 citing papers in PubMed.

  1. eLife · 2026
    Article
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  5. Review
  6. Article
  7. Calmodulin assists during co-translational folding of the KProtein science : a publication of the Protein Society · 2026
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  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Ribosome-associated quality control and related mechanisms.Nature structural & molecular biology · 2026
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Vivekanandan Shanmuganathan *Gene Center, Department of Biochemistry, Center for integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Munich, Germany.
Nina Schiller *Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Anastasia MagoulopoulouDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Jingdong ChengGene Center, Department of Biochemistry, Center for integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Munich, Germany.
Katharina BraungerGene Center, Department of Biochemistry, Center for integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Munich, Germany.ORCID 0000-0002-9067-2155
Florian CymerDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Otto BerninghausenGene Center, Department of Biochemistry, Center for integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Munich, Germany.
Birgitta BeatrixGene Center, Department of Biochemistry, Center for integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Munich, Germany.
Kenji KohnoInstitute for Research Initiatives, Nara Institute of Science and Technology, Takayama, Japan.ORCID 0000-0002-3503-6551
Gunnar von HeijneDepartment of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.ORCID 0000-0002-4490-8569
Roland BeckmannGene Center, Department of Biochemistry, Center for integrated Protein Science Munich (CiPSM), Ludwig-Maximilians-Universität München, Munich, Germany.ORCID 0000-0003-4291-3898

Funding

Boehringer Ingelheim Fonds Graduate FellowshipCancerfonden 15 0888Deutsche Forschungsgemeinschaft GRK1721Deutsche Forschungsgemeinschaft QBM (Quantitative Biosciences Munich) Graduate School FellowshipJapan Society for the Promotion of Science JP26116006Knut och Alice Wallenbergs Stiftelse 2012.0282Vetenskapsrådet 621-2014-3713
6 · The paper itself

Abstract

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 Å 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.

Indexed as

Amino Acid SequenceAnimalsBiomechanical PhenomenaDNA Mutational AnalysisEndoribonucleasesHumansModels, MolecularMutagenesisPeptidesPeptidyl TransferasesProtein BindingProtein Serine-Threonine KinasesProtein StabilityRabbitsRibosomesSEC Translocation ChannelsEndoribonucleasesERN1 protein, humanPeptidesPeptidyl TransferasesProtein Serine-Threonine KinasesSEC Translocation ChannelsSignal Recognition ParticleX-Box Binding Protein 1biochemistrychemical biologymolecular biophysicsribosomestructural biologytranslational pausingXBP1

Identifiers

PMID31246176
PMCPMC6624018

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.