Academic Journal
Cryo-EM Structure of the C. Elegans Septin Tetramer Reveals a Revised Architecture and Conserved Positional Orthology.
| Τίτλος: | Cryo-EM Structure of the C. Elegans Septin Tetramer Reveals a Revised Architecture and Conserved Positional Orthology. |
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| Συγγραφείς: | Saladino GCDR; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil., Ciol H; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil., Mendonça DC; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil., Furtado AA; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil., Pereira HD; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil., Klaholz BP; Centre for Integrative Biology (CBI), Institute of Genetics and Molecular and Cellular Biology, CNRS/Inserm/University of Strasbourg, 67404 Illkirch, France., Ulian Araujo AP; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil. Electronic address: anapaula@ifsc.usp.br., Garratt RC; Sao Carlos Institute of Physics, University of Sao Paulo, IFSC - USP, Avenida Joao Dagnone, 1100, 13566-590 Sao Carlos, SP, Brazil. Electronic address: richard@ifsc.usp.br. |
| Πηγή: | Journal of molecular biology [J Mol Biol] 2026 Oct 01; Vol. 438 (19), pp. 169915. Date of Electronic Publication: 2026 Jun 23. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 2985088R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1089-8638 (Electronic) Linking ISSN: 00222836 NLM ISO Abbreviation: J Mol Biol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: 1959- : London : Academic Press |
| Ιατρικοί όροι (MeSH): | Caenorhabditis elegans*/metabolism , Cryoelectron Microscopy*/methods , Caenorhabditis elegans Proteins*/chemistry , Caenorhabditis elegans Proteins*/metabolism , Caenorhabditis elegans Proteins*/genetics , Caenorhabditis elegans Proteins*/ultrastructure , Septins*/chemistry , Septins*/metabolism , Septins*/genetics , Septins*/ultrastructure, Animals ; Models, Molecular ; Protein Multimerization ; Humans |
| Περίληψη: | Septins are cytoskeletal proteins that assemble into hetero-oligomeric complexes, which polymerize into filaments to regulate many cellular processes, including cytokinesis and membrane remodeling. In Caenorhabditis elegans, the core septin complex is a tetramer composed of two copies each of two different subunits, UNC-59 and UNC-61. Historically, low-resolution models suggested a subunit order of UNC-59-UNC-61-UNC-61-UNC-59 for the tetramer. However, this arrangement contradicted the positional conservation of septins observed in other species. Using cryo-EM, we obtained a structure for the tetramer with a global resolution of 2.7 Å, definitively establishing the subunit order to be UNC-61-UNC-59-UNC-59-UNC-61. This places UNC-59 at the center of the particle where it forms a homodimeric G-interface, confirming it to be a positional ortholog of human SEPT7. This arrangement is further supported by mutational/biophysical analyses. Despite the stability of the tetramer, the complex failed to polymerize into filaments in vitro, which we attribute to the structural instability of the terminal UNC-61 G-interfaces. Our results suggest that post-translational modifications or specific cellular factors may be required to initiate higher-order assembly in C. elegans. Furthermore, our structure reveals that while UNC-59 possesses key characteristics of the SEPT7 group, it also features unique structural adaptations that may be related to the unique arrangement of the C. elegans complex. We demonstrate that the previous misidentification of the subunit order within the tetramer likely stemmed from N-terminal domain swapping, reinforcing the importance of high-resolution structural studies for understanding the evolutionary history and the diversity of septins. (Copyright © 2026 The Author(s). Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: C. elegans; cryo-electron microscopy; protein–protein interfaces; septins |
| Substance Nomenclature: | 0 (Caenorhabditis elegans Proteins) EC 3.6.1.- (Septins) |
| Entry Date(s): | Date Created: 20260623 Date Completed: 20260806 Latest Revision: 20260806 |
| Update Code: | 20260807 |
| DOI: | 10.1016/j.jmb.2026.169915 |
| PMID: | 42336232 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1089-8638 |
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| DOI: | 10.1016/j.jmb.2026.169915 |