Wyszukiwarka
Molecular mechanism and energetics of coupling between substrate binding and product release in the F 1 -ATPase catalytic cycle
Abstrakt
F1-ATPase is a motor protein that couples the rotation of its rotary γ subunit with ATP synthesis or hydrolysis. Single-molecule experiments indicate that nucleotide binding and release events occur almost simultaneously during the synthesis cycle, allowing the energy gain due to spontaneous binding of ADP to one catalytic β subunit to be directly harnessed for driving the release of ATP from another rather than being dissipated as heat. Here, we examine the unknown mechanism of this coupling that is critical for an exceptionally high mechanochemical efficiency of F1-ATPase by means of all-atom free-energy simulations. We find that nondissipative and kinetically fast progression of the motor in the synthesis direction requires a concerted conformational change involving the closure of the ADP-binding β subunit followed by the gradual opening of the ATP-releasing β subunit over the course of the 30 to 40° rotary substep of the γ subunit. This rotary substep, preceding the ATP-dependent metastable state, allows for the recovery of a large portion of the ADP binding energy in the conformation of ATP-bound β that gradually adopts the low-affinity conformation, captured also by the recent cryo-EM structure of this elusive state. The release of ATP from this nearly open conformation leads to its further opening, which enables the progression of the motor to the next catalytic metastable state. Our simulations explain this energy conversion mechanism in terms of intersubunit and ligand–protein interactions.
Cytowania
-
1
CrossRef
-
0
Web of Science
-
1
Scopus
Autorzy (6)
-
Helmut Grubmüller
-
Cytuj jako
Pełna treść
- Wersja publikacji
- Accepted albo Published Version
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1073/pnas.2215650120
- Licencja
-
otwiera się w nowej karcie
Słowa kluczowe
Informacje szczegółowe
- Kategoria:
- Publikacja w czasopiśmie
- Typ:
- artykuły w czasopismach
- Opublikowano w:
-
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
nr 120,
ISSN: 0027-8424 - Język:
- angielski
- Rok wydania:
- 2023
- Opis bibliograficzny:
- Badocha M., Wieczór M., Marciniak A., Kleist C., Grubmüller H., Czub J.: Molecular mechanism and energetics of coupling between substrate binding and product release in the F 1 -ATPase catalytic cycle// PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA -Vol. 120,iss. 8 (2023),
- DOI:
- Cyfrowy identyfikator dokumentu elektronicznego (otwiera się w nowej karcie) 10.1073/pnas.2215650120
- Źródła finansowania:
-
- Połowę kosztów APC poniosła jednostka współpracująca
- IDUB
- Weryfikacja:
- Politechnika Gdańska
wyświetlono 119 razy
Publikacje, które mogą cię zainteresować
Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS
- C. Kutzner,
- J. Czub,
- H. Grubmüller