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Molecular basis for protection of ribosomal protein L4 from cellular degradation

Huber, Ferdinand M. and Hoelz, André (2017) Molecular basis for protection of ribosomal protein L4 from cellular degradation. Nature Communications, 8 . Art. No. 14354. ISSN 2041-1723. PMCID PMC5296656.

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[img] Video (QuickTime) (Morphing of the Acl4•RpL4 complex to the conformations of Acl4 apo and RpL4 as found in the 60S large ribosomal subunit. Acl4 and RpL4 are shown in cartoon representation and colored according to Fig. 1) - Supplemental Material
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Eukaryotic ribosome biogenesis requires the nuclear import of ∼80 nascent ribosomal proteins and the elimination of excess amounts by the cellular degradation machinery. Assembly chaperones recognize nascent unassembled ribosomal proteins and transport them together with karyopherins to their nuclear destination. We report the crystal structure of ribosomal protein L4 (RpL4) bound to its dedicated assembly chaperone of L4 (Acl4), revealing extensive interactions sequestering 70 exposed residues of the extended RpL4 loop. The observed molecular recognition fundamentally differs from canonical promiscuous chaperone–substrate interactions. We demonstrate that the eukaryote-specific RpL4 extension harbours overlapping binding sites for Acl4 and the nuclear transport factor Kap104, facilitating its continuous protection from the cellular degradation machinery. Thus, Acl4 serves a dual function to facilitate nuclear import and simultaneously protect unassembled RpL4 from the cellular degradation machinery.

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Hoelz, André0000-0003-1726-0127
Additional Information:© 2017 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit Received: 29 June 2016. Accepted: 19 December 2016. Published online: 02 February 2017. We thank Daniel H. Lin, Alina Patke and Emily J. Rundlet, for critical reading of the manuscript, Raymond J. Deshaies, Min-Kyung Sung, and Andrew M. Davenport for helpful discussions, Christopher Markosian for technical support, Jens Kaiser and the scientific staff of SSRL Beamline 12-2 for their support with X-ray diffraction measurements and Yuh Min Chook and Raymond J. Deshaies for sharing material. The operations at SSRL are supported by the Department of Energy and the National Institutes of Health. We acknowledge the Gordon and Betty Moore Foundation, the Beckman Institute, and the Sanofi-Aventis Bioengineering Research Program for their support of the Molecular Observatory at the California Institute of Technology. F.M.H. was supported by a PhD fellowship of the Boehringer Ingelheim Fonds. A.H. is a Faculty Scholar of the Howard Hughes Medical Institute, an inaugural Principal Investigator of the Heritage Medical Research Institute for the Advancement of Medicine and Science at Caltech and was supported by Caltech startup funds, a Kimmel Scholar Award of the Sidney Kimmel Foundation for Cancer Research, and a Teacher-Scholar Award of the Camille & Henry Dreyfus Foundation. Author Contributions: F.M.H. and A.H. conceived of the project, designed the experiments, analysed the data and wrote the manuscript. F.M.H. performed the experiments. Data availability: The coordinates and structure factors have been deposited with the Protein Data Bank with accession codes 5TQB (Acl4·RpL4) and 5TQC (Kap104·RpL4EXT). The data that support the findings of this study are available from the corresponding author on request. The authors declare no competing financial interests. Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Group:Heritage Medical Research Institute
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Department of Energy (DOE)UNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Caltech Sanofi-Aventis Bioengineering Research ProgramUNSPECIFIED
Boehringer Ingelheim FondsUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
Sidney Kimmel Foundation for Cancer ResearchUNSPECIFIED
Camille and Henry Dreyfus FoundationUNSPECIFIED
PubMed Central ID:PMC5296656
Record Number:CaltechAUTHORS:20170202-153010885
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Official Citation:Huber, F. M. & Hoelz, A. Molecular basis for protection of ribosomal protein L4 from cellular degradation. Nat. Commun. 8, 14354 doi: 10.1038/ncomms14354 (2017).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73995
Deposited By: George Porter
Deposited On:02 Feb 2017 23:44
Last Modified:16 Apr 2020 18:25

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