Asset Details
Do you wish to reserve the book?
Bending forces and nucleotide state jointly regulate F-actin structure
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Bending forces and nucleotide state jointly regulate F-actin structure
Do you wish to request the book?
Bending forces and nucleotide state jointly regulate F-actin structure
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Bending forces and nucleotide state jointly regulate F-actin structure
2022
Overview
ATP-hydrolysis-coupled actin polymerization is a fundamental mechanism of cellular force generation
1
–
3
. In turn, force
4
,
5
and actin filament (F-actin) nucleotide state
6
regulate actin dynamics by tuning F-actin’s engagement of actin-binding proteins through mechanisms that are unclear. Here we show that the nucleotide state of actin modulates F-actin structural transitions evoked by bending forces. Cryo-electron microscopy structures of ADP–F-actin and ADP-P
i
–F-actin with sufficient resolution to visualize bound solvent reveal intersubunit interfaces bridged by water molecules that could mediate filament lattice flexibility. Despite extensive ordered solvent differences in the nucleotide cleft, these structures feature nearly identical lattices and essentially indistinguishable protein backbone conformations that are unlikely to be discriminable by actin-binding proteins. We next introduce a machine-learning-enabled pipeline for reconstructing bent filaments, enabling us to visualize both continuous structural variability and side-chain-level detail. Bent F-actin structures reveal rearrangements at intersubunit interfaces characterized by substantial alterations of helical twist and deformations in individual protomers, transitions that are distinct in ADP–F-actin and ADP-P
i
–F-actin. This suggests that phosphate rigidifies actin subunits to alter the bending structural landscape of F-actin. As bending forces evoke nucleotide-state dependent conformational transitions of sufficient magnitude to be detected by actin-binding proteins, we propose that actin nucleotide state can serve as a co-regulator of F-actin mechanical regulation.
The nucleotide state of actin modulates F-actin structural transitions evoked by bending forces.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 96/34
/ 96/63
/ Actin
/ Actin Cytoskeleton - chemistry
/ Actin Cytoskeleton - metabolism
/ Actin Cytoskeleton - ultrastructure
/ Adenosine Diphosphate - chemistry
/ Adenosine Diphosphate - metabolism
/ Bending
/ Binding
/ Humanities and Social Sciences
/ Lattices
/ Microfilament Proteins - metabolism
/ Proteins
/ Science
/ Solvents
