Electrostatic interactions between the Bni1p formin FH2 domain and actin influence actin filament nucleation

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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Formins catalyze nucleation and growth of actin filaments. Here, 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. 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.

Original languageEnglish (US)
Pages (from-to)68-79
Number of pages12
JournalStructure
Volume23
Issue number1
DOIs
StatePublished - Jan 6 2015

Bibliographical note

Funding Information:
J.L.B., D.L.P., and G.A.V. were supported by the National Science Foundation (NSF) through the Center for Multiscale Theory and Simulation (grant CHE-1136709 ). M.M. was supported by a Ruth L. Kirschstein National Research Service Award ( GM101848 ) from the National Institute of General Medical Sciences . N.C. and T.D.P. were supported by NIH research grant GM-026338 (awarded to T.D.P.) and a postdoctoral fellowship from the Leukemia and Lymphoma Society (awarded to N.C.). Simulations were performed using the Extreme Science and Engineering Discovery Environment, which is supported by NSF grant OCI-1053575 . This research also used resources of the Argonne Leadership Computing Facility (ALCF) and the ALCF-2 Early Science Program at the Argonne National Laboratory, which is supported by the U.S. Department of Energy Office of Science under contract DE-AC02-06CH11357 .

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