Skip to main content
SpringerLink
Log in

A model for the chemomechanical coupling of the mammalian cytoplasmic dynein molecular motor

  • Original Article
  • Published:
European Biophysics Journal Aims and scope Submit manuscript

Abstract

Available single-molecule data have shown that some mammalian cytoplasmic dynein dimers move on microtubules with a constant step size of about 8.2 nm. Here, a model is presented for the chemomechanical coupling of these mammalian cytoplasmic dynein dimers. In contrast to the previous models, a peculiar feature of the current model is that the rate constants of ATPase activity are independent of the external force. Based on this model, analytical studies of the motor dynamics are presented. With only four adjustable parameters, the theoretical results reproduce quantitatively diverse available single-molecule data on the force dependence of stepping ratio, velocity, mean dwell time, and dwell-time distribution between two mechanical steps. Predicted results are also provided for the force dependence of the number of ATP molecules consumed per mechanical step, indicating that under no or low force the motors exhibit a tight chemomechanical coupling, and as the force increases the number of ATPs consumed per step increases greatly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Allan VJ (2011) Cytoplasmic dynein. Biochem Soc Trans 39:1169–1178

    Article  CAS  PubMed  Google Scholar 

  • Bameta T, Padinhateeri R, Inamdar MM (2013) Force generation and step-size fluctuations in a dynein motor. J Stat Mech 2:02030

    Google Scholar 

  • Bhabha G, Johnson GT, Schroeder CM, Vale RD (2016) How dynein moves along microtubules. Trends Biochem Sci 41:94–105

    Article  CAS  PubMed  Google Scholar 

  • Carter AP, Garbarino JE, Wilson-Kubalek EM, Shipley WE, Cho C, Milligan RA, Vale RD, Gibbons IR (2008) Structure and functional role of dynein’s microtubule-binding domain. Science 322:1691–1695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carter AP, Cho C, Jin L, Vale RD (2011) Crystal structure of the dynein motor domain. Science 331:1159–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DeWitt M, Chang A, Combs P, Yildiz A (2012) Cytoplasmic dynein moves through uncoordinated stepping of the AAA+ ring domains. Science 335:221–225

    Article  CAS  PubMed  Google Scholar 

  • Gennerich A, Carter A, Reck-Peterson S, Vale RD (2007) Force-induced bidirectional stepping of cytoplasmic dynein. Cell 131:952–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gibbons IR, Gibbons BH, Mocz G, Asai DJ (1991) Multiple nucleotide binding sites in the sequence of dynein beta heavy chain. Nature 352:640–643

    Article  CAS  PubMed  Google Scholar 

  • Gibbons IR, Garbarino JE, Tan CE, Reck-Peterson SL, Vale RD, Carter AP (2005) The affinity of the dynein microtubule-binding domain is modulated by the conformation of its coiled-coil stalk. J Biol Chem 280:23960–23965

    Article  CAS  PubMed  Google Scholar 

  • Imamula K, Kon T, Ohkura R, Sutoh K (2007) The coordination of cyclic microtubule association/dissociation and tail swing of cytoplasmic dynein. Proc Natl Acad Sci USA 104:16134–16139

    Article  PubMed  PubMed Central  Google Scholar 

  • Kon T, Imamula K, Roberts AJ, Ohkura R, Knight PJ, Gibbons IR, Burgess SA, Sutoh K (2009) Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding. Nat Struct Mol Biol 16:325–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kon T, Sutoh K, Kurisu G (2011) X-ray structure of a functional full-length dynein motor domain. Nat Struct Mol Biol 18:638–642

    Article  CAS  PubMed  Google Scholar 

  • Kon T, Oyama T, Shimo-Kon R, Imamula K, Shima T, Sutoh K, Kurisu G (2012) The 2.8 Å crystal structure of the dynein motor domain. Nature 484:345–350

    Article  CAS  PubMed  Google Scholar 

  • Morikawa M, Yajima H, Nitta R, Inoue S, Ogura T, Sato C, Hirokawa N (2015) X-ray and Cryo-EM structures reveal mutual conformational changes of Kinesin and GTP-state microtubules upon binding. EMBO J 34:1270–1286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mukherji S (2008) Model for the unidirectional motion of a dynein molecule. Phys Rev E 77:051916

    Article  CAS  Google Scholar 

  • Nicholas MP, Hook P, Gennerich A (2015) Control of cytoplasmic dynein force production and processivity by its C-terminal domain. Nat Commun 6:6206

    Article  CAS  PubMed  Google Scholar 

  • Qiu W, Derr N, Goodman B, Villa E, Wu D, Shih W, Reck-Peterson S (2012) Dynein achieves processive motion using both stochastic and coordinated stepping. Nat Struct Mol Biol 19:193–200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raaijmakers JA, Medema RH (2014) Function and regulation of dynein in mitotic chromosome segregation. Chromosoma 123:407–422

    Article  CAS  PubMed  Google Scholar 

  • Reck-Peterson S, Yildiz A, Carter A, Gennerich A, Zhang N, Vale RD (2006) Single-molecule analysis of dynein processivity and stepping behavior. Cell 126:335–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Redwine WB, Hernández-López R, Zou S, Huang J, Reck-Peterson SL, Leschziner AE (2012) Structural basis for microtubule binding and release by dynein. Science 337:1532–1536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts AJ, Numata N, Walker ML, Kato YS, Malkova B, Kon T, Ohkura R, Arisaka F, Knight PJ, Sutoh K, Burgess SA (2009) AAA+ ring and linker swing mechanism in the dynein motor. Cell 136:485–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts AJ, Kon T, Knight PJ, Sutoh K, Burgess SA (2013) Functions and mechanics of dynein motor proteins. Nat Rev Mol Cell Biol 14:713–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakamoto T, Webb MR, Forgacs E, White HD, Sellers JR (2008) Direct observation of the mechanochemical coupling in myosin Va during processive movement. Nature 455:128–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarlah A, Vilfan A (2014) The winch model can explain both coordinated and uncoordinated stepping of cytoplasmic dynein. Biophys J 107:662–671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki K, Kaya M, Higuchi H (2018) A unified walking model for dimeric motor proteins. Biophys J 115:1–12

    Article  CAS  Google Scholar 

  • Schmidt H (2015) Dynein motors: how AAA+ ring opening and closing coordinates microtubule binding and linker movement. BioEssays 37:532–543

    Article  CAS  PubMed  Google Scholar 

  • Schmidt H, Gleave ES, Carter AP (2012) Insights into dynein motor domain function from a 3.3-Å crystal structure. Nat Struct Mol Biol 19:492–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt H, Zalyte R, Urnavicius L, Carter AP (2015) Structure of human cytoplasmic dynein-2 primed for its power stroke. Nature 518:435–438

    Article  CAS  PubMed  Google Scholar 

  • Shi X-X, Fu Y-B, Guo S-K, Wang P-Y, Chen H, Xie P (2018) Investigating role of conformational changes of microtubule in regulating its binding affinity to kinesin by all-atom molecular dynamics simulation. Proteins 86:1127–1139

    Article  CAS  PubMed  Google Scholar 

  • Singh MP, Mallik R, Gross SP, Yu CC (2005) Monte Carlo modeling of single molecule cytoplasmic dynein. Proc Natl Acad Sci USA 102:12059–12064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sumathy S, Satyanarayana SVM (2015) Model for bidirectional movement of cytoplasmic dynein. J Theor Biol 380:48–52

    Article  CAS  PubMed  Google Scholar 

  • Toba S, Watanabe T, Yamaguchi-Okimoto L, Toyoshima Y, Higuchi H (2006) Overlapping hand-over-hand mechanism of single molecular motility of cytoplasmic dynein. Proc Natl Acad Sci USA 103:5741–5745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trott L, Hafezparast M, Madzvamuse A (2018) A mathematical understanding of how cytoplasmic dynein walks on microtubules. R Soc Open Sci 5:171568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsygankov D, Serohijos A, Dokholyan N, Elston T (2011) A physical model reveals the mechanochemistry responsible for dynein’s processive motion. Biophys J 101:144–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uchimura S, Fujii T, Takazaki H et al (2015) A flipped ion pair at the dynein-microtubule interface is critical for dynein motility and ATPase activation. J Cell Biol 208:211–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie P (2010) Mechanism of processive movement of monomeric and dimeric kinesin molecules. Int J Biol Sci 6:665–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie P, Chen H (2018) A non-tight chemomechanical coupling model for force-dependence of movement dynamics of molecular motors. Phys Chem Chem Phys 20:4752–4759

    Article  CAS  PubMed  Google Scholar 

  • Xie P, Dou S-X, Wang P-Y (2006) Model for unidirectional movement of axonemal and cytoplasmic dynein molecules. Acta Biochim Biophys Sin 38:711–724

    Article  CAS  PubMed  Google Scholar 

  • Xie P, Guo S-K, Chen H (2019) ATP-concentration- and force-dependent chemomechanical coupling of kinesin molecular motors. J Chem Inf Model 59:360–372

    Article  CAS  PubMed  Google Scholar 

  • Yildiz A, Tomishige M, Gennerich A, Vale RD (2008) Intramolecular strain coordinates kinesin stepping behavior along microtubules. Cell 134:1030–1041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao XY, Sun W, Zhang JP, Tala Guo WS (2014) A model for the coordinated stepping of cytoplasmic dynein. Biochem Biophys Res Commun 453:686–691

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant no. 11775301).

Author information

Authors and Affiliations

  1. Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China

    Ping Xie

Authors
  1. Ping Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ping Xie.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 156 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xie, P. A model for the chemomechanical coupling of the mammalian cytoplasmic dynein molecular motor. Eur Biophys J 48, 609–619 (2019). https://doi.org/10.1007/s00249-019-01386-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00249-019-01386-z

Keywords

Search

Navigation