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

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2014 Dec 9

PMID 25482541

Citations 16

Authors

Joseph L Baker

Naomi Courtemanche

Daniel L Parton

Martin McCullagh

Thomas D Pollard

Gregory A Voth

Affiliations

Soon will be listed here.

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.

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References

Kang H, Bradley M, McCullough B, Pierre A, Grintsevich E, Reisler E . Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness. Proc Natl Acad Sci U S A. 2012; 109(42):16923-7. PMC: 3479481. DOI: 10.1073/pnas.1211078109. View

Courtemanche N, Pollard T . Determinants of Formin Homology 1 (FH1) domain function in actin filament elongation by formins. J Biol Chem. 2012; 287(10):7812-20. PMC: 3293521. DOI: 10.1074/jbc.M111.322958. View

Kang H, Bradley M, Elam W, De La Cruz E . Regulation of actin by ion-linked equilibria. Biophys J. 2013; 105(12):2621-8. PMC: 3882474. DOI: 10.1016/j.bpj.2013.10.032. View

Kovar D, Kuhn J, Tichy A, Pollard T . The fission yeast cytokinesis formin Cdc12p is a barbed end actin filament capping protein gated by profilin. J Cell Biol. 2003; 161(5):875-87. PMC: 2172974. DOI: 10.1083/jcb.200211078. View

Zigmond S, Evangelista M, Boone C, Yang C, Dar A, Sicheri F . Formin leaky cap allows elongation in the presence of tight capping proteins. Curr Biol. 2003; 13(20):1820-3. DOI: 10.1016/j.cub.2003.09.057. View

Xu Y, Moseley J, Sagot I, Poy F, Pellman D, Goode B . Crystal structures of a Formin Homology-2 domain reveal a tethered dimer architecture. Cell. 2004; 116(5):711-23. DOI: 10.1016/s0092-8674(04)00210-7. View

Higashida C, Miyoshi T, Fujita A, Oceguera-Yanez F, Monypenny J, Andou Y . Actin polymerization-driven molecular movement of mDia1 in living cells. Science. 2004; 303(5666):2007-10. DOI: 10.1126/science.1093923. View

MacKerell Jr A, Feig M, Brooks 3rd C . Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem. 2004; 25(11):1400-15. DOI: 10.1002/jcc.20065. View

Kovar D, Pollard T . Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. Proc Natl Acad Sci U S A. 2004; 101(41):14725-30. PMC: 522035. DOI: 10.1073/pnas.0405902101. View

10.

Dominguez R . Actin-binding proteins--a unifying hypothesis. Trends Biochem Sci. 2004; 29(11):572-8. DOI: 10.1016/j.tibs.2004.09.004. View

11.

Romero S, Clainche C, Didry D, Egile C, Pantaloni D, Carlier M . Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell. 2004; 119(3):419-29. DOI: 10.1016/j.cell.2004.09.039. View

12.

Schutt C, Myslik J, Rozycki M, Goonesekere N, Lindberg U . The structure of crystalline profilin-beta-actin. Nature. 1993; 365(6449):810-6. DOI: 10.1038/365810a0. View

13.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View

14.

Chang F, Drubin D, Nurse P . cdc12p, a protein required for cytokinesis in fission yeast, is a component of the cell division ring and interacts with profilin. J Cell Biol. 1997; 137(1):169-82. PMC: 2139860. DOI: 10.1083/jcb.137.1.169. View

15.

McGough A, Pope B, Chiu W, Weeds A . Cofilin changes the twist of F-actin: implications for actin filament dynamics and cellular function. J Cell Biol. 1997; 138(4):771-81. PMC: 2138052. DOI: 10.1083/jcb.138.4.771. View

16.

Vinson V, De La Cruz E, Higgs H, Pollard T . Interactions of Acanthamoeba profilin with actin and nucleotides bound to actin. Biochemistry. 1998; 37(31):10871-80. DOI: 10.1021/bi980093l. View

17.

Otomo T, Tomchick D, Otomo C, Panchal S, Machius M, Rosen M . Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain. Nature. 2005; 433(7025):488-94. DOI: 10.1038/nature03251. View

18.

Kuhn J, Pollard T . Real-time measurements of actin filament polymerization by total internal reflection fluorescence microscopy. Biophys J. 2004; 88(2):1387-402. PMC: 1305141. DOI: 10.1529/biophysj.104.047399. View

19.

Chu J, Voth G . Allostery of actin filaments: molecular dynamics simulations and coarse-grained analysis. Proc Natl Acad Sci U S A. 2005; 102(37):13111-6. PMC: 1201585. DOI: 10.1073/pnas.0503732102. View

20.

Phillips J, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E . Scalable molecular dynamics with NAMD. J Comput Chem. 2005; 26(16):1781-802. PMC: 2486339. DOI: 10.1002/jcc.20289. View