Computational modeling highlights the role of the disordered Formin Homology 1 domain in profilin-actin transfer

Horan, Brandon G.; Zerze, Gül H.; Kim, Young C.; Vavylonis, Dimitrios; Mittal, Jeetain

doi:10.1002/1873-3468.13088

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

Journal Article · Sun May 13 00:00:00 EDT 2018 · FEBS Letters

DOI:https://doi.org/10.1002/1873-3468.13088· OSTI ID:1543443

^[1]; Zerze, Gül H. ^[1]; Kim, Young C. ^[2]; Vavylonis, Dimitrios ^[1]; Mittal, Jeetain ^[1]

Lehigh Univ., Bethlehem, PA (United States)
Naval Research Lab. (NRL), Washington, DC (United States)

Formins accelerate actin polymerization, assumed to occur through flexible Formin Homology 1 (FH1) domain-mediated transfer of profilin-actin to the barbed end. To investigate 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 discover that 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.

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Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH); National Science Foundation (NSF)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1543443

Journal Information:: FEBS Letters, Vol. 592, Issue 11; ISSN 0014-5793

Publisher:: Federation of European Biochemical SocietiesCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 14 works

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59 BASIC BIOLOGICAL SCIENCES
actin polymerization
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Dataset for: Computational modeling highlights disordered Formin Homology 1 domain's role in profilin-actin transfer Horan, Brandon Gregory; Zerze, Gül H.; Kim, Young C. https://doi.org/10.6084/M9.FIGSHARE.6217361 The current record is supplemented by this dataset	dataset	January 2018
Dataset for: Computational modeling highlights disordered Formin Homology 1 domain's role in profilin-actin transfer Horan, Brandon Gregory; Zerze, Gül H.; Kim, Young C. https://doi.org/10.6084/m9.figshare.6217361.v1 The current record is supplemented by this dataset	dataset	January 2018
Dataset for: Computational modeling highlights disordered Formin Homology 1 domain's role in profilin-actin transfer Horan, Brandon Gregory; Zerze, Gül H.; Kim, Young C. https://doi.org/10.6084/m9.figshare.c.4088999 The current record is supplemented by this collection	collection	January 2018
Dataset for: Computational modeling highlights disordered Formin Homology 1 domain's role in profilin-actin transfer Horan, Brandon Gregory; Zerze, Gül H.; Kim, Young C. https://doi.org/10.6084/m9.figshare.c.4088999.v1 The current record is supplemented by this collection	collection	January 2018