skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Computational modeling highlights the role of the disordered Formin Homology 1 domain in profilin‐actin transfer

Abstract

Formins accelerate actin polymerization, assumed to occur through flexible Formin Homology 1 (FH1) domain‐mediated transfer of profilin‐actin to the barbed end. To study FH1 properties and address sequence effects, including varying length/distribution of profilin‐binding proline‐rich motifs, we performed all‐atom simulations of a set of representative FH1 domains of formins: mouse mDia1 and mDia2, budding yeast Bni1 and Bnr1, and fission yeast Cdc12, For3, and Fus1. We find FH1 has flexible regions between high‐propensity polyproline helix regions. A coarse‐grained model retaining sequence specificity, assuming rigid polyproline segments, describes their size. Multiple bound profilins or profilin‐actin complexes expand mDia1‐FH1, which may be important in cells. Simulations of the barbed end bound to Bni1‐FH1‐FH2 dimer show that the leading FH1 can better transfer profilin or profilin‐actin, with decreasing probability as the distance from FH2 increases.

Authors:
ORCiD logo [1];  [2];  [3];  [1];  [2]
  1. Department of Physics Lehigh University Bethlehem PA USA
  2. Department of Chemical and Biomolecular Engineering Lehigh University Bethlehem PA USA
  3. Center for Materials Physics and Technology Naval Research Laboratory Washington DC USA
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1543443
DOE Contract Number:  
AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
FEBS Letters
Additional Journal Information:
Journal Volume: 592; Journal Issue: 11; Journal ID: ISSN 0014-5793
Publisher:
Federation of European Biochemical Societies
Country of Publication:
United States
Language:
English
Subject:
Biochemistry & Molecular Biology; Biophysics; Cell Biology

Citation Formats

Horan, Brandon G., Zerze, Gül H., Kim, Young C., Vavylonis, Dimitrios, and Mittal, Jeetain. Computational modeling highlights the role of the disordered Formin Homology 1 domain in profilin‐actin transfer. United States: N. p., 2018. Web. doi:10.1002/1873-3468.13088.
Horan, Brandon G., Zerze, Gül H., Kim, Young C., Vavylonis, Dimitrios, & Mittal, Jeetain. Computational modeling highlights the role of the disordered Formin Homology 1 domain in profilin‐actin transfer. United States. doi:10.1002/1873-3468.13088.
Horan, Brandon G., Zerze, Gül H., Kim, Young C., Vavylonis, Dimitrios, and Mittal, Jeetain. Thu . "Computational modeling highlights the role of the disordered Formin Homology 1 domain in profilin‐actin transfer". United States. doi:10.1002/1873-3468.13088.
@article{osti_1543443,
title = {Computational modeling highlights the role of the disordered Formin Homology 1 domain in profilin‐actin transfer},
author = {Horan, Brandon G. and Zerze, Gül H. and Kim, Young C. and Vavylonis, Dimitrios and Mittal, Jeetain},
abstractNote = {Formins accelerate actin polymerization, assumed to occur through flexible Formin Homology 1 (FH1) domain‐mediated transfer of profilin‐actin to the barbed end. To study FH1 properties and address sequence effects, including varying length/distribution of profilin‐binding proline‐rich motifs, we performed all‐atom simulations of a set of representative FH1 domains of formins: mouse mDia1 and mDia2, budding yeast Bni1 and Bnr1, and fission yeast Cdc12, For3, and Fus1. We find FH1 has flexible regions between high‐propensity polyproline helix regions. A coarse‐grained model retaining sequence specificity, assuming rigid polyproline segments, describes their size. Multiple bound profilins or profilin‐actin complexes expand mDia1‐FH1, which may be important in cells. Simulations of the barbed end bound to Bni1‐FH1‐FH2 dimer show that the leading FH1 can better transfer profilin or profilin‐actin, with decreasing probability as the distance from FH2 increases.},
doi = {10.1002/1873-3468.13088},
journal = {FEBS Letters},
issn = {0014-5793},
number = 11,
volume = 592,
place = {United States},
year = {2018},
month = {5}
}