Work

Remodelling of Rea1 linker domain drives the removal of assembly factors from pre-ribosomal particles

Year: 2024

Type: article

Abstract: The ribosome maturation factor Rea1 (or Midasin) catalyses the removal of assembly factors from large ribosomal subunit precursors and promotes their export from the nucleus to the cytosol. Rea1 consists of nearly 5000 amino-acid residues and belongs to the AAA+ protein family. It consists of a ring of six AAA+ domains from which the ≈1700 amino-acid residue linker emerges that is subdivided into stem, middle and top domains. A flexible and unstructured D/E rich region connects the linker top to a MIDAS (metal ion dependent adhesion site) domain, which is able to bind the assembly factor substrates. Despite its key importance for ribosome maturation, the mechanism driving assembly factor removal by Rea1 is still poorly understood. Here we demonstrate that the Rea1 linker is essential for assembly factor removal. It rotates and swings towards the AAA+ ring following a complex remodelling scheme involving nucleotide independent as well as nucleotide dependent steps. ATP-hydrolysis is required to engage the linker with the AAA+ ring and ultimately with the AAA+ ring docked MIDAS domain. The interaction between the linker top and the MIDAS domain allows direct force transmission for assembly factor removal.

Source: Nature Communications

DOI: 10.1038/s41467-024-54698-w

Authors: Johan Busselez, Geraldine Koenig, Carine Dominique, Torben Klos, Deepika Velayudhan, Piotr Sosnowski, Nils Marechal, Corinne Crucifix, Hugo Gizardin-Fredon, Sarah Cianferani, Benjamin Albert, Yves Henry, Anthony K. Henras, Helgo Schmidt

Institutions: Centre National de la Recherche Scientifique, Inserm, Institut de génétique et de biologie moléculaire et cellulaire, Université de Strasbourg, Université de Toulouse, Unité de biologie Moléculaire, Cellulaire et du Développement, Centre de Biologie Intégrative de Toulouse, Institut Pluridisciplinaire Hubert Curien

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,790

Funders: Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Université de Strasbourg, Centre National de la Recherche Scientifique, French Infrastructure for Integrated Structural Biology

Awards: G1109023570, G1194865751, Infrastructure Française de Protéomique, G1502922282, G191178678, G1923432458, Par-delà les frontières, l'Université de Strasbourg, G2255650664, G2447855386, G2449524460, G2659019386, G2694206344, Façonner les talents en formation et en recherche à l'Université de Strasbourg, G2980570810, G3010527862, G3310169441, G3357951378, G3730343, G399734812, G4460985483, Integrative Molecular and Cellular Biology, G471331628, G4779185514, G4798114250, G4899307531, G4964816082, Integrative Biology : Nuclear dynamics- Regenerative medicine - Translational medicine, G5605099691, G6136357505, Ribosome biogenesis: The yin and yang of protein homeostasis, G6803667113, G7002111755, G7240651115, Structural and functional investigations on Rea1 complexes, G7804020939, Infrastructure Française pour la Biologie Structurale Intégrée, G8996902167

OpenAlex ID: W4404789504

FWCI: 0.116

Cites: 46

Cited by: 1

Related to: 10