Electrostatic Interactions between the Bni1p Formin FH2 Domain and Actin Influence Actin Filament Nucleation

Baker, Joseph L.; Courtemanche, Naomi; Parton, Daniel L.; McCullagh, Martin; Pollard, Thomas D.; Voth, Gregory A.

doi:10.1016/j.str.2014.10.014

Title: Electrostatic Interactions between the Bni1p Formin FH2 Domain and Actin Influence Actin Filament Nucleation

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Abstract

Formins catalyze nucleation and growth of actin filaments. In this paper, we study the structure and interactions of actin with the FH2 domain of budding yeast formin Bni1p. We built an all-atom model of the formin dimer on an Oda actin filament 7-mer and studied structural relaxation and interprotein interactions by molecular dynamics simulations. These simulations produced a refined model for the FH2 dimer associated with the barbed end of the filament and showed electrostatic interactions between the formin knob and actin target-binding cleft. Mutations of two formin residues contributing to these interactions (R1423N, K1467L, or both) reduced the interaction energies between the proteins, and in coarse-grained simulations, the formin lost more interprotein contacts with an actin dimer than with an actin 7-mer. Finally, biochemical experiments confirmed a strong influence of these mutations on Bni1p-mediated actin filament nucleation, but not elongation, suggesting that different interactions contribute to these two functions of formins.

Authors:: Baker, Joseph L.; Courtemanche, Naomi; Parton, Daniel L.; McCullagh, Martin; Pollard, Thomas D.; Voth, Gregory A.

Publication Date:: Thu Jan 01 00:00:00 EST 2015

Research Org.:: Univ. of Chicago, IL (United States)

Sponsoring Org.:: USDOE Office of Science (SC)

OSTI Identifier:: 1242545

Alternate Identifier(s):: OSTI ID: 1233908; OSTI ID: 1344507

Grant/Contract Number:: AC02-06CH11357

Resource Type:: Published Article

Journal Name:: Structure

Additional Journal Information:: Journal Name: Structure Journal Volume: 23 Journal Issue: 1; Journal ID: ISSN 0969-2126

Publisher:: Elsevier

Country of Publication:: United Kingdom

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES

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                    Baker, Joseph L., Courtemanche, Naomi, Parton, Daniel L., McCullagh, Martin, Pollard, Thomas D., and Voth, Gregory A. Electrostatic Interactions between the Bni1p Formin FH2 Domain and Actin Influence Actin Filament Nucleation.  United Kingdom: N. p., 2015. 
Web.  doi:10.1016/j.str.2014.10.014.

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                    Baker, Joseph L., Courtemanche, Naomi, Parton, Daniel L., McCullagh, Martin, Pollard, Thomas D., & Voth, Gregory A. Electrostatic Interactions between the Bni1p Formin FH2 Domain and Actin Influence Actin Filament Nucleation.  United Kingdom.  https://doi.org/10.1016/j.str.2014.10.014

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                    Baker, Joseph L., Courtemanche, Naomi, Parton, Daniel L., McCullagh, Martin, Pollard, Thomas D., and Voth, Gregory A. Thu .  
"Electrostatic Interactions between the Bni1p Formin FH2 Domain and Actin Influence Actin Filament Nucleation".  United Kingdom.  https://doi.org/10.1016/j.str.2014.10.014.

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@article{osti_1242545,

  title        = {Electrostatic Interactions between the Bni1p Formin FH2 Domain and Actin Influence Actin Filament Nucleation},

  author       = {Baker, Joseph L. and Courtemanche, Naomi and Parton, Daniel L. and McCullagh, Martin and Pollard, Thomas D. and Voth, Gregory A.},

  abstractNote = {Formins catalyze nucleation and growth of actin filaments. In this paper, we study the structure and interactions of actin with the FH2 domain of budding yeast formin Bni1p. We built an all-atom model of the formin dimer on an Oda actin filament 7-mer and studied structural relaxation and interprotein interactions by molecular dynamics simulations. These simulations produced a refined model for the FH2 dimer associated with the barbed end of the filament and showed electrostatic interactions between the formin knob and actin target-binding cleft. Mutations of two formin residues contributing to these interactions (R1423N, K1467L, or both) reduced the interaction energies between the proteins, and in coarse-grained simulations, the formin lost more interprotein contacts with an actin dimer than with an actin 7-mer. Finally, biochemical experiments confirmed a strong influence of these mutations on Bni1p-mediated actin filament nucleation, but not elongation, suggesting that different interactions contribute to these two functions of formins.},

  doi          = {10.1016/j.str.2014.10.014},

  journal      = {Structure},

  number       = 1,

  volume       = 23,

  place        = {United Kingdom},

  year         = {Thu Jan 01 00:00:00 EST 2015},

  month        = {Thu Jan 01 00:00:00 EST 2015}

}

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