Phosphorylation of P-stalk proteins defines the ribosomal state for interaction with auxiliary protein factors
Ribosomal action is facilitated by the orchestrated work of trans-acting factors and ribosomal elements, which are subject to regulatory events, often involving phosphorylation. One such element is the ribosomal P-stalk, which plays a dual function: it activates translational GTPases, which support basic ribosomal functions, and interacts with the Gcn2 kinase, linking the ribosomes to the ISR pathway. We show that P-stalk proteins, which form a pentamer, exist in the cell exclusively in a phosphorylated state at five C-terminal domains (CTDs), ensuring optimal translation (speed and accuracy) and may play a role in the timely regulation of the Gcn2-dependent stress response. Phosphorylation of the CTD induces a structural transition from a collapsed to a coil-like structure, and the CTD gains conformational freedom, allowing specific but transient binding to various protein partners, optimizing the ribosome action. The report reveals a unique feature of the P-stalk proteins, indicating that, unlike most ribosomal proteins, which are regulated by phosphorylation in an on/off manner, the P-stalk proteins exist in a constantly phosphorylated state, which optimizes their interaction with auxiliary factors.
Authors
- Eliza Molestak (ORCID: https://orcid.org/0000-0002-6595-7351)
- Lidia Borkiewicz (ORCID: https://orcid.org/0000-0002-2834-0969)
- Sebastian Kmiecik (ORCID: https://orcid.org/0000-0001-7623-0935)
- Agata L. Starosta (ORCID: https://orcid.org/0000-0003-3915-5723)
- Yutian Shao
- Mateusz Mołoń (ORCID: https://orcid.org/0000-0002-9962-6788)
- Mateusz Zalewski (ORCID: https://orcid.org/0000-0002-3436-8829)
- Konrad Kubiński (ORCID: https://orcid.org/0000-0001-6870-845X)
- Dawid Krokowski
- Barbara Michalec‐Wawiórka
- Marina V. Rodnina (ORCID: https://orcid.org/0000-0003-0105-3879)
- Patrycja Horbowicz‐Drożdżal
- Piotr Właź (ORCID: https://orcid.org/0000-0002-5389-0241)
- Leszek Wawiórka (ORCID: https://orcid.org/0000-0003-1363-817X)
- Sandra Blanchet (ORCID: https://orcid.org/0000-0001-7804-7739)
- Kamil Filipek (ORCID: https://orcid.org/0000-0002-3139-5901)
- Colin Chih‐Chien Wu (ORCID: https://orcid.org/0000-0002-6013-0224)
- Katarzyna Socała (ORCID: https://orcid.org/0000-0001-7706-2080)
- Rachel Green (ORCID: https://orcid.org/0000-0001-9337-2003)
- Marek Tchórzewski (ORCID: https://orcid.org/0000-0002-0718-4223)
- Kyle W. Cunningham (ORCID: https://orcid.org/0000-0001-6877-6321)
- Monika Zaciura
- Przemysław Grela (ORCID: https://orcid.org/0000-0002-5930-416X)
- Przemysław Latoch (ORCID: https://orcid.org/0000-0001-7561-4718)
- Alan González-Ibarra
Institutions
- John Paul II Catholic University of Lublin (PL)
- Medical University of Lublin (PL)
- Centre National de la Recherche Scientifique (FR)
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Maria Curie-Skłodowska University (PL)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Université Paris-Saclay (FR)
- Johns Hopkins Medicine (US)
- Max Planck Institute for the Study of Religious and Ethnic Diversity (DE)
- Institut de Biologie Intégrative de la Cellule (FR)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL)
- CEA Paris-Saclay (FR)
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- University of Warsaw (PL)
- University of Rzeszów (PL)
Publication Details
- Journal
- EMBO Reports
- Published
- 2024-10-28
- DOI
- https://doi.org/10.1038/s44319-024-00297-1
- Citations
- 8
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft
- Leibniz-Gemeinschaft