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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041121 | PMC |
| http://dx.doi.org/10.1002/1873-3468.13088 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Sequential recruitment of F-BAR proteins controls cytoskeletal crosstalk at the yeast bud neck.
Curr Biol
January 2025
Department of Biology, Rosenstiel Basic Medical Science Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA. Electronic address:
In vivo functions of the septin and actin cytoskeletons are closely intertwined, yet the mechanisms underlying septin-actin crosstalk have remained poorly understood. Here, we show that the yeast-bud-neck-associated Fes/CIP4 homology Bar-amphiphysin-Rvs (F-BAR) protein suppressor of yeast profilin 1 (Syp1)/FCHo uses its intrinsically disordered region (IDR) to directly bind and bundle filamentous actin (F-actin) and to physically link septins and F-actin. Interestingly, the only other F-BAR protein found at the neck during bud development, Hof1, has related activities and also potently inhibits the bud-neck-associated formin Bnr1.
View Article and Find Full Text PDFHuman formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes.
bioRxiv
October 2024
Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, California, 90095.
Article Synopsis
- Actin cytoskeleton assembly is crucial for cell movement and muscle contraction, with formins being key proteins that help in the creation and maintenance of actin filaments.
- The FHOD-family of formins, particularly FHOD3L, is essential for developing sarcomeres in heart cells (cardiomyocytes), yet its precise functions are not fully understood.
- Research shows that FHOD3L is involved in nucleating and briefly elongating actin filaments, and its elongation activity is vital for proper sarcomere structure and function, which has implications for understanding heart muscle diseases.
Methylation and phosphorylation of formin homology domain proteins (Fhod1 and Fhod3) by protein arginine methyltransferase 7 (PRMT7) and Rho kinase (ROCK1).
J Biol Chem
November 2024
Department of Chemistry and Biochemistry, University of California, Los Angeles, California, USA; Molecular Biology Institute, University of California - Los Angeles, Los Angeles, California, USA. Electronic address:
Protein post-translational modifications (PTMs) can regulate biological processes by altering an amino acid's bulkiness, charge, and hydrogen bonding interactions. Common modifications include phosphorylation, methylation, acetylation, and ubiquitylation. Although a primary focus of studying PTMs is understanding the effects of a single amino acid modification, the possibility of additional modifications increases the complexity.
View Article and Find Full Text PDFFHOD-1 and profilin protect sarcomeres against contraction-induced deformation> in .
Mol Biol Cell
November 2024
Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210.
Formin HOmology Domain 2-containing (FHOD) proteins are a subfamily of actin-organizing formins important for striated muscle development in many animals. We showed previously that absence of the sole FHOD protein, FHOD-1, from results in thin body wall muscles with misshapen dense bodies that serve as sarcomere Z-lines. We demonstrate here that mutations predicted to specifically disrupt actin polymerization by FHOD-1 similarly disrupt muscle development, and that FHOD-1 cooperates with profilin PFN-3 for dense body morphogenesis, and with profilins PFN-2 and PFN-3 to promote body wall muscle growth.
View Article and Find Full Text PDFIdentification of an FMNL2 Interactome by Quantitative Mass Spectrometry.
Int J Mol Sci
May 2024
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Formin Homology Proteins (Formins) are a highly conserved family of cytoskeletal regulatory proteins that participate in a diverse range of cellular processes. FMNL2 is a member of the Diaphanous-Related Formin sub-group, and previous reports suggest FMNL2's role in filopodia assembly, force generation at lamellipodia, subcellular trafficking, cell-cell junction assembly, and focal adhesion formation. How FMNL2 is recruited to these sites of action is not well understood.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!