CoChat
Sign Up
PreprintCited by 29Protein Structure and DynamicsCellular Mechanics and InteractionsAdvanced Physical and Chemical Molecular Interactions

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Insights into the cooperative nature of ATP hydrolysis in actin filaments

Open access
Katkar, Harshwardhan H., Davtyan, Aram, Durumeric, Aleksander E. P., Hocky, Glen M., Schramm, Anthony C., De La Cruz, Enrique M., Voth, Gregory A.·2018·Biophysical Journal
DOI 10.1101/319558PMC PMC6260209

Preprint — published as 10.1016/j.bpj.2018.08.034

Open this paper in CoChat — free accountOpen PDF

Abstract

Actin filaments continually assemble and disassemble within a cell. Assembled filaments “age” as a bound nucleotide ATP within each actin subunit quickly hydrolyzes, followed by a slower release of the phosphate P i , leaving behind a bound ADP. This subtle change in nucleotide state of actin subunits affects filament rigidity as well as its interactions with binding partners. We present here a systematic multiscale ultra-coarse-graining (UCG) approach that provides a computationally efficient way to simulate a long actin filament undergoing ATP hydrolysis and phosphate release reactions, while systematically taking into account available atomistic details. The slower conformational changes and their dependence on the chemical reactions are simulated with the UCG model by assigning internal states to the coarse-grained sites. Each state is represented by a unique potential surface of a local heterogeneous elastic network. Internal states undergo stochastic transitions that are coupled to conformations of the underlying molecular system. The UCG model reproduces mechanical properties of the filament and allows us to study whether fluctuations in actin subunits produce cooperative aging in the filament. Our model predicts that nucleotide state of neighboring subunit significantly modulates the reaction kinetics, implying cooperativity in ATP hydrolysis and P i release. We further systematically coarse-grain the system into a Markov state model that incorporates assembly and disassembly, facilitating a direct comparison with previously published models. We find that cooperativity in ATP hydrolysis and P i release significantly affects the filament growth dynamics only near the critical G-actin monomer concentration, while both cooperative and random mechanisms show similar growth dynamics far from the critical concentration. In contrast, filament composition in terms of the bound nucleotide distribution varies significantly at all monomer concentrations studied. These results provide new insights into the cooperative nature of ATP hydrolysis and P i release and the implications it has for actin filament properties, providing novel predictions for future experimental studies.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/319558

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 61

  1. 10.1038/347037a0 · DOI
  2. 10.1021/bi011214b · DOI
  3. 10.1074/jbc.M601973200 · DOI
  4. 10.1016/j.jmb.2011.07.068 · DOI
  5. 10.1021/ja507169f · DOI
  6. 2017, Simulating Protein Mediated Hydrolysis of ATP and Other Nucleoside Triphosphates by Combining QM/MM Molecular Dynamics with Advances in Metadynamics, J. Chem. Theory Comput, 13, 2332, 10.1021/acs.jctc.7b00077 · DOI
  7. 10.1083/jcb.103.6.2747 · DOI
  8. 1987, The Mechanisms of Atp Hydrolysis Accompanying the Polymerization of Mg-actin and Ca-actin, J. Biol. Chem, 262, 3052, 10.1016/S0021-9258(18)61467-X · DOI
  9. 1977, Mechanism of Atp Hydrolysis by Polymer Actin, Biophys. Chem, 7, 51, 10.1016/0301-4622(77)87014-2 · DOI
  10. 1984, Evidence That F-actin Can Hydrolyze Atp Independent of Monomer-polymer End Interactions, J. Biol. Chem, 259, 1441, 10.1016/S0021-9258(17)43426-0 · DOI
  11. 10.1016/0014-5793(84)81376-9 · DOI
  12. 1986, The Effects of Mg-2+ at the High-affinity and Low-affinity Sites on the Polymerization of Actin and Associated Atp Hydrolysis, J. Biol. Chem, 261, 785
  13. 10.1021/bi00372a001 · DOI
  14. 10.1016/0006-291X(87)90361-5 · DOI
  15. 1988, Binding of Phosphate to F-adp-actin and Role of F-adp-Pi-actin in Atp-actin Polymerization, J. Biol. Chem, 263, 817, 10.1016/S0021-9258(19)35428-6 · DOI
  16. 10.1016/0014-5793(88)81264-X · DOI
  17. 10.1021/bi961325o · DOI
  18. 10.1016/0022-2836(92)90520-T · DOI
  19. 10.1073/pnas.1211078109 · DOI
  20. 10.1016/j.bpj.2013.10.032 · DOI
  21. 2016, Cations Stiffen Actin Filaments by Adhering a Key Structural Element to Adjacent Subunits, J. Phys. Chem. B, 120, 4558, 10.1021/acs.jpcb.6b02741 · DOI
  22. 10.1074/jbc.270.19.11437 · DOI
  23. 10.1529/biophysj.108.139733 · DOI
  24. 10.1529/biophysj.105.073924 · DOI
  25. 2012, Coarse-Graining Provides Insights on the Essential Nature of Heterogeneity in Actin Filaments, Biophys. J, 103, 1334, 10.1016/j.bpj.2012.08.029 · DOI
  26. 10.1016/j.str.2012.02.008 · DOI
  27. Prinz, J. H. , H. Wu , M. Sarich , B. Keller , M. Senne , M. Held , J. D. Chodera , C. Schutte , and F. Noe . 2011. Markov models of molecular kinetics: Generation and validation. J. Chem. Phys. 134. · DOI · Paper page
  28. Bowman, G. R. , V. Pande , and F. Noe . 2014. An introduction to Markov State Models and their application to long timescale molecular simulation. Springer, Dordrecht. · DOI
  29. Nuske, F. , H. Wu , J. H. Prinz , C. Wehmeyer , C. Clementi , and F. Noe . 2017. Markov state models from short non-equilibrium simulations-Analysis and correction of estimation bias. J. Chem. Phys. 146. · DOI
  30. 10.1073/pnas.0501435102 · DOI
  31. 10.1529/biophysj.105.074211 · DOI
  32. 2014, The Theory of Ultra-Coarse-Graining. 2. Numerical Implementation, J. Chem. Theory Comput, 10, 5265, 10.1021/ct500834t · DOI
  33. 2017, The Theory of Ultra-Coarse-Graining. 3. Coarse-Grained Sites with Rapid Local Equilibrium of Internal States, J. Chem. Theory Comput, 13, 1010, 10.1021/acs.jctc.6b01081 · DOI
  34. 2018, Ultra-Coarse-Grained Models Allow for an Accurate and Transferable Treatment of Interfacial Systems, J. Chem. Theory Comput, 14, 2180, 10.1021/acs.jctc.7b01173 · DOI
  35. 10.1073/pnas.0702510104 · DOI
  36. 2011, Individual Actin Filaments in a Microfluidic Flow Reveal the Mechanism of Atp Hydrolysis and Give Insight into the Properties of Profilin, PLOS Biol, 9, 1001161, 10.1371/journal.pbio.1001161 · DOI
  37. 10.1021/bi9527045 · DOI
  38. 10.1073/pnas.82.21.7207 · DOI
  39. 10.1126/science.3672117 · DOI
  40. 1994, Mechanism of Atp Hydrolysis by Polymeric Actin, Biochim. Biophys. Acta, Protein Struct. Mol. Enzymol, 1208, 8, 10.1016/0167-4838(94)90153-8 · DOI
  41. 2010, Role of Atp-hydrolysis in the Dynamics of a Single Actin Filament, Biophys. J, 98, 1418, 10.1016/j.bpj.2009.12.4306 · DOI
  42. 10.1002/jcc.20291 · DOI
  43. 10.1038/nature07685 · DOI
  44. 10.1073/pnas.0902092106 · DOI
  45. 10.1016/0263-7855(96)00018-5 · DOI · Paper page
  46. 10.1002/jcc.20289 · DOI · Paper page
  47. Bussi, G. , D. Donadio , and M. Parrinello . 2007. Canonical sampling through velocity rescaling. J. Chem. Phys. 126. · DOI
  48. 2014, Nucleotide Regulation of the Structure and Dynamics of G-Actin, Biophys. J, 106, 1710, 10.1016/j.bpj.2014.03.012 · DOI
  49. 1995, Fast Parallel Algorithms for Short-Range Molecular-Dynamics, J. Comput. Phys, 117, 1, 10.1006/jcph.1995.1039 · DOI · Paper page
  50. 10.1016/j.jmb.2008.05.055 · DOI
  51. 10.1016/j.jmb.2009.11.034 · DOI
  52. 10.1126/science.1059700 · DOI
  53. 10.1074/jbc.M303689200 · DOI
  54. 10.1073/pnas.0503732102 · DOI
  55. 10.1016/j.jmb.2013.01.020 · DOI
  56. 10.1021/ja01607a027 · DOI
  57. 10.1046/j.1432-1327.1998.2510538.x · DOI · Paper page
  58. 1998, Recovery of free ADP, P-i, and free energy of ATP hydrolysis in human skeletal muscle, J. Appl. Physiol, 85, 2140, 10.1152/jappl.1998.85.6.2140 · DOI
  59. 10.1021/jp0761665 · DOI · Paper page
  60. 10.1016/j.cub.2011.03.064 · DOI · Paper page
  61. 10.1016/j.bpj.2017.05.016 · DOI

Cited by

Sorted by citations

Metadata

Authors
Katkar, H. H., Davtyan, A., Durumeric, A. E. P., Hocky, G. M., Schramm, A. C., De La Cruz, E. M., & Voth, G. A.
Affiliations
  • University of Chicago (US)
  • Yale University (US)
Corresponding author
Voth, Gregory A.
ORCID
Venue
Biophysical Journal
Publisher
openRxiv
Published
2018-05-10
Volume
115
Issue
8
Pages
1589-1602
ISSN
0006-3495 (ISSN-L)
DOI
10.1101/319558
PMC
PMC6260209
OpenAlex
W2949314358
Cited by
29
References
1
Citations by year
2026: 2 · 2025: 2 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 3 · 2018: 2
FWCI
1.69
Type
journal article
Language
en
Open access
Locations
  • Biophysical Journal (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation (1420709, ACI-1 548 562, 1548562)
  • U.S. Department of Defense (W911NF1410403)
  • University of Chicago (DMR-1420709)
  • National Institutes of Health
  • Materials Research Science and Engineering Center, Harvard University (1420709, ACI-1548562, DMR 1420709)
  • National Defense Science and Engineering Graduate
  • Multidisciplinary University Research Initiative (W911NF-14-1-0403)
  • National Institute of General Medical Sciences (ACI1548562, R01GM097348, F32 GM11345-01, 1548562)
  • Division of Materials Research (1420709., DMR 14- 20709, ACI-1548562)
  • Army Research Office (W911NF-14-1-0403, ACI-1548562)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Advanced Physical and Chemical Molecular Interactions
Keywords
F-actin, ATP hydrolysis, phosphate release, nucleotide state, Markov state models, conformational fluctuations
MeSH terms
Actins, Adenosine Diphosphate, Adenosine Triphosphate, Humans, Hydrolysis, Kinetics, Actin Cytoskeleton, Phosphates

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review