Molecular basis for protection of ribosomal protein L4 from cellular degradation
Ferdinand M. Huber & André Hoelz
Nature Communications 8, Article number: 14354 (2017)
Chaperones Ribosomal proteins Structural biology
Received: 29 June 2016 Accepted: 19 December 2016 Published online: 02 February 2017
Figure 1: Analysis of the Acl4·RpL4 structure.
Abstract
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.
Acknowledgements
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 information
Affiliations
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA
Ferdinand M. Huber & André Hoelz
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.
Competing interests
The authors declare no competing financial interests.
Corresponding author
Correspondence to André Hoelz.
