Home LiteratureArticle Details
PMID: 11463615 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Thermodynamics and kinetics of actin filament nucleation.

Biophysical journal ·Vol. 81 ·No. 2 ·2001-08-00 ·Pages 667-74

Sept D, McCammon JA

Abstract

We have performed computer simulations and free energy calculations to determine the thermodynamics and kinetics of actin nucleation and thus identify a probable nucleation pathway and critical nucleus size. The binding free energies of structures along the nucleation pathway are found through a combination of electrostatic calculations and estimates of the entropic and surface area contributions. The association kinetics for the formation of each structure are determined through a series of Brownian dynamics simulations. The combination of the binding free energies and the association rate constants determines the dissociation rate constants, allowing for a complete characterization of the nucleation and polymerization kinetics. The results indicate that the trimer is the size of the critical nucleus, and the rate constants produce polymerization plots that agree very well with experimental results over a range of actin monomer concentrations.

MeSH Terms
Actin Cytoskeleton/chemistry,metabolism Actins/chemistry,metabolism Adenosine Triphosphate/metabolism Biopolymers/chemistry,metabolism Cations, Divalent/metabolism Computer Simulation Diffusion Kinetics Models, Biological Models, Molecular Protein Structure, Quaternary Rotation Thermodynamics
Chemicals
Actins Biopolymers Cations, Divalent Adenosine Triphosphate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sept D
Center for Computational Biology, Washington University, St. Louis, Missouri. 63130-4899, USA. [email protected]
McCammon J A
References (36)
36 references, click to expand
  1. Scar, a WASp-related protein, activates nucleation of actin filaments by the Arp2/3 complex.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3739-44 PMID: 10097107
  2. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly.
    Cell. 1999 Apr 16;97(2):221-31 PMID: 10219243
  3. Activation of the yeast Arp2/3 complex by Bee1p, a WASP-family protein.
    Curr Biol. 1999 May 6;9(9):501-4 PMID: 10322115
  4. The Wiskott-Aldrich syndrome protein directs actin-based motility by stimulating actin nucleation with the Arp2/3 complex.
    Curr Biol. 1999 May 20;9(10):555-8 PMID: 10339430
  5. Divalent cation-, nucleotide-, and polymerization-dependent changes in the conformation of subdomain 2 of actin.
    Biophys J. 1999 Jul;77(1):373-85 PMID: 10388764
  6. Computer simulation of protein-protein association kinetics: acetylcholinesterase-fasciculin.
    J Mol Biol. 1999 Aug 6;291(1):149-62 PMID: 10438612
  7. Influence of the C terminus of Wiskott-Aldrich syndrome protein (WASp) and the Arp2/3 complex on actin polymerization.
    Biochemistry. 1999 Nov 16;38(46):15212-22 PMID: 10563804
  8. Computer modeling of electrostatic steering and orientational effects in antibody-antigen association.
    Biophys J. 1995 Mar;68(3):807-14 PMID: 7756548
  9. Yeast actin: polymerization kinetic studies of wild type and a poorly polymerizing mutant.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):91-5 PMID: 8552682
  10. The determinants of pKas in proteins.
    Biochemistry. 1996 Jun 18;35(24):7819-33 PMID: 8672483
  11. The statistical-thermodynamic basis for computation of binding affinities: a critical review.
    Biophys J. 1997 Mar;72(3):1047-69 PMID: 9138555
  12. Entropy in protein folding and in protein-protein interactions.
    Curr Opin Struct Biol. 1997 Apr;7(2):215-21 PMID: 9094326
  13. Experimental measurement of the effective dielectric in the hydrophobic core of a protein.
    Biophys Chem. 1997 Feb 28;64(1-3):211-24 PMID: 9127946
  14. Simulation of the diffusional association of barnase and barstar.
    Biophys J. 1997 May;72(5):1917-29 PMID: 9129797
  15. The entropy cost of protein association.
    J Mol Biol. 1997 Nov 14;273(5):1048-60 PMID: 9367790
  16. Brownian dynamics simulation of protein-protein diffusional encounter.
    Methods. 1998 Mar;14(3):329-41 PMID: 9571088
  17. The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):6181-6 PMID: 9600938
  18. Interaction of human Arp2/3 complex and the Listeria monocytogenes ActA protein in actin filament nucleation.
    Science. 1998 Jul 3;281(5373):105-8 PMID: 9651243
  19. Computer simulations of actin polymerization can explain the barbed-pointed end asymmetry.
    J Mol Biol. 1999 Dec 17;294(5):1181-9 PMID: 10600376
  20. Polymerization and structure of nucleotide-free actin filaments.
    J Mol Biol. 2000 Jan 21;295(3):517-26 PMID: 10623543
  21. Activation by Cdc42 and PIP(2) of Wiskott-Aldrich syndrome protein (WASp) stimulates actin nucleation by Arp2/3 complex.
    J Cell Biol. 2000 Sep 18;150(6):1311-20 PMID: 10995437
  22. Kinetics of the cooperative association of actin to actin filaments.
    Biophys Chem. 1975 Jul;3(3):215-25 PMID: 1174645
  23. The kinetics of actin nucleation and polymerization.
    J Biol Chem. 1983 Mar 10;258(5):3207-14 PMID: 6826559
  24. Kinetic evidence for a monomer activation step in actin polymerization.
    Biochemistry. 1983 Apr 26;22(9):2193-202 PMID: 6860660
  25. Polymerization of actin: mechanism of the Mg2+-induced process at pH 8 and 20 degrees C.
    Proc Natl Acad Sci U S A. 1983 Nov;80(21):6513-7 PMID: 6579538
  26. Polymerization of actin and actin-like systems: evaluation of the time course of polymerization in relation to the mechanism.
    Biochemistry. 1983 Dec 6;22(25):5836-43 PMID: 6661414
  27. Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments.
    J Cell Biol. 1986 Dec;103(6 Pt 2):2747-54 PMID: 3793756
  28. Actin.
    Curr Opin Cell Biol. 1990 Feb;2(1):33-40 PMID: 2183841
  29. Atomic model of the actin filament.
    Nature. 1990 Sep 6;347(6288):44-9 PMID: 2395461
  30. Actin: protein structure and filament dynamics.
    J Biol Chem. 1991 Jan 5;266(1):1-4 PMID: 1985885
  31. Reconciling the magnitude of the microscopic and macroscopic hydrophobic effects.
    Science. 1991 Apr 5;252(5002):106-9 PMID: 2011744
  32. Thermodynamics of actin polymerization; influence of the tightly bound divalent cation and nucleotide.
    Biochim Biophys Acta. 1991 Apr 8;1077(2):151-8 PMID: 2015289
  33. Tightly-bound divalent cation of actin.
    J Muscle Res Cell Motil. 1992 Jun;13(3):272-84 PMID: 1527214
  34. Calculation of the free energy of association for protein complexes.
    Protein Sci. 1992 Jan;1(1):169-81 PMID: 1339024
  35. Co-operativity in protein-protein association. The structure and stability of the actin filament.
    J Mol Biol. 1989 Apr 5;206(3):465-74 PMID: 2716058
  36. Effects of charged amino acid mutations on the bimolecular kinetics of reduction of yeast iso-1-ferricytochrome c by bovine ferrocytochrome b5.
    Biochemistry. 1993 Jul 6;32(26):6613-23 PMID: 8392365
Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(01)75731-1
Email
[email protected]
Published
2001-08-00
Pages
667-74
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1301543
Subset
IM
External Links
PubMed source DOI: 10.1016/S0006-3495(01)75731-1 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2