ABCE1 Controls Ribosome Recycling by an Asymmetric Dynamic Conformational Equilibrium

Gouridis, Giorgos; Hetzert, Bianca; Kiosze-Becker, Kristin; Boer, Marijnde; Heinemann, Holger; Nürenberg-Goloub, Elina; Cordes, Thorben and Tampé, Robert (2019): ABCE1 Controls Ribosome Recycling by an Asymmetric Dynamic Conformational Equilibrium. In: Cell reports, Vol. 28, No. 3, e6: pp. 723-734

Abstract

The twin-ATPase ABCE1 has a vital function in mRNA translation by recycling terminated or stalled ribosomes. As for other functionally distinct ATP-binding cassette (ABC) proteins, the mechanochemical coupling of ATP hydrolysis to conformational changes remains elusive. Here, we use an integrated biophysical approach allowing direct observation of conformational dynamics and ribosome association of ABCE1 at the single-molecule level. Our results from FRET experiments show that the current static two-state model of ABC proteins has to be expanded because the two ATP sites of ABCE1 are in dynamic equilibrium across three distinct conformational states: open, intermediate, and closed. The interaction of ABCE1 with ribosomes influences the conformational dynamics of both ATP sites asymmetrically and creates a complex network of conformational states. Our findings suggest a paradigm shift to redefine the understanding of the mechanochemical coupling in ABC proteins: from structure-based deterministic models to dynamic-based systems.

• Item Type: Journal article
• EU Funded Grant Agreement Number: 638536
• EU Projects: Horizon 2020 > ERC Grants > ERC Starting Grant > ERC Grant 638536: SM-IMPORT - Substrate import at work: single-molecule studies of ABC transporters
• Faculties: Biology > Department Biology I
• Subjects: 500 Science > 570 Life sciences; biology
• Language: English