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@ARTICLE{Mello:639659,
author = {Mello, Victor Hugo and Wald, Jiri and Marlovits, Thomas and
Sartori, Pablo},
title = {{E}lastic analysis bridges structure and dynamics of an
{AAA}+ molecular motor},
journal = {PLoS Computational Biology},
volume = {21},
number = {10},
issn = {1553-734X},
address = {San Francisco, Calif.},
publisher = {Public Library of Science},
reportid = {PUBDB-2025-04616},
pages = {e1013596 -},
year = {2025},
abstract = {Proteins carry out cellular functions by changing their
structure among a few conformations, each characterised by a
different energy level. Therefore, structural changes,
energy transformations, and protein function are intimately
related. Despite its central importance, this relationship
remains elusive. For example, while many hexameric ATPase
motors are known to function using a hand-over-hand
alternation of subunits, how energy transduction throughout
the assembly’s structure drives the hand-over-hand
mechanism is not known. In this work, we unravel the
energetic basis of hand-over-hand in a model AAA+ motor,
RuvB. To do so, we develop a general method to compute the
residue-scale elastic pseudoenergy due to structure changes
and apply it to RuvB structures, recently resolved through
cryo-EM. This allows us to quantify how progression through
RuvB’s mechanochemical cycle translates into residue-scale
energy transduction. In particular, we find that DNA binding
is associated with overcoming a high energy barrier. This is
possible through inter-subunit transmission of energy, and
ultimately driven by nucleotide exchange. Furthermore, we
show how this structure-inferred energetic quantification
can be integrated into a non-equilibrium model of AAA+
assembly dynamics, consistent with single-molecule
biophysics measurements. Overall, our work elucidates the
energetic basis for the hand-over-hand mechanism in RuvB’s
cycle. Besides, it presents a generally applicable
methodology for studying the energetics of conformational
cycles in other proteins, allowing to quantitatively bridge
data from structural biology and single-molecule
biophysics.},
cin = {CSSB-UKE-TM},
ddc = {610},
cid = {I:(DE-H253)CSSB-UKE-TM-20210520},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633)},
pid = {G:(DE-HGF)POF4-633},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
doi = {10.1371/journal.pcbi.1013596},
url = {https://bib-pubdb1.desy.de/record/639659},
}