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@ARTICLE{Wald:486215,
author = {Wald, Jiri and Fahrenkamp, Dirk and Goessweiner-Mohr,
Nikolaus and Lugmayr, Wolfgang and Ciccarelli, Luciano and
Vesper, Oliver and Marlovits, Thomas},
title = {{M}echanism of {AAA}+ {ATP}ase-mediated
{R}uv{AB}–{H}olliday junction branch migration},
journal = {Nature},
volume = {609},
number = {7927},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {PUBDB-2022-07157},
pages = {630 - 639},
year = {2022},
abstract = {The Holliday junction is a key intermediate formed during
DNA recombination across all kingdoms of life1. In bacteria,
the Holliday junction is processed by two homo-hexameric
AAA+ ATPase RuvB motors, which assemble together with the
RuvA–Holliday junction complex to energize the
strand-exchange reaction2. Despite its importance for
chromosome maintenance, the structure and mechanism by which
this complex facilitates branch migration are unknown. Here,
using time-resolved cryo-electron microscopy, we obtained
structures of the ATP-hydrolysing RuvAB complex in seven
distinct conformational states, captured during assembly and
processing of a Holliday junction. Five structures together
resolve the complete nucleotide cycle and reveal the
spatiotemporal relationship between ATP hydrolysis,
nucleotide exchange and context-specific conformational
changes in RuvB. Coordinated motions in a converter formed
by DNA-disengaged RuvB subunits stimulate hydrolysis and
nucleotide exchange. Immobilization of the converter enables
RuvB to convert the ATP-contained energy into a lever
motion, which generates the pulling force driving the branch
migration. We show that RuvB motors rotate together with the
DNA substrate, which, together with a progressing nucleotide
cycle, forms the mechanistic basis for DNA recombination by
continuous branch migration. Together, our data decipher the
molecular principles of homologous recombination by the
RuvAB complex, elucidate discrete and sequential
transition-state intermediates for chemo-mechanical coupling
of hexameric AAA+ motors and provide a blueprint for the
design of state-specific compounds targeting AAA+ motors.},
cin = {FS-CS / CSSB-UKE-TM},
ddc = {500},
cid = {I:(DE-H253)FS-CS-20210408 /
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},
pubmed = {pmid:36002576},
UT = {WOS:000844487700001},
doi = {10.1038/s41586-022-05121-1},
url = {https://bib-pubdb1.desy.de/record/486215},
}