Septins: comparative studies and the correlation between structure and function

• Grant number: 14/15546-1
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2015
• End date: January 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Richard Charles Garratt
• Grantee: Richard Charles Garratt
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Pesquisadores principais: Ana Paula Ulian de Araujo
• Associated researchers: Claudia Elisabeth Munte ; Humberto D'Muniz Pereira ; Katia Cristina Pereira Oliveira Santos ; Marcos Vicente de Albuquerque Salles Navarro ; Ricardo de Marco ; Rodrigo Villares Portugal ; Rosangela Itri
• Associated research grant(s): 15/16811-3 - Multi-user equipament aproved in grant 2014:15546-1: crystallization robot Gryphon, AP.EMU; 15/16812-0 - Multi-User Equipment approved in grant 2014/15546-1: SEC-MALS, AP.EMU
• Associated scholarship(s): 18/12268-1 - Support activities for cloning and DNA sequencing, BP.TT; 18/03906-4 - Support activities for mass spectrometry, BP.TT; 17/07709-6 - Use of low resolution techniques for structural analysis of septin filaments, BP.PD; + associated scholarships 17/05665-1 - Structural studies of septin hetero-complexes by electron microscopy, BP.PD; 16/19734-2 - Molecular recognition in septins: the interface studies between SEPT7 and SEPT12, BP.MS; 16/13961-7 - Interactions of Schistosoma mansoni septins with membrane models, BP.MS; 16/04658-9 - Structural determinants for specific interaction of interfaces G and NC of septins: validating the substitution rules in the assembly of the filament, BP.DR; 13/20715-4 - Studies of the correlation between septin dynamics and Ca2+ homeostasis in muscular cells from Schistosoma mansoni, BP.PD - associated scholarships

Abstract

The present proposal focuses on structural and functional aspects of the septin family of proteins using an integrated approach involving a series of biophysical and cellular techniques. Despite having been described for the first time 40 years ago in yeast, where they are essential for completing the cell cycle, septins are still considered a neglected component of the cytoskeleton in terms of their biochemistry and physiology. For example, little is known concerning the factors which control the formation of a septin hetero-filament and how this is related to GTP binding, GTP hydrolysis and membrane association. Furthermore, only one crystal structure of the dozens of possible combinations for a hetero-filament has been described to date, and that at low resolution. Even less is known about septins from lower organisms. The current research proposal is divided into three sub-projects dealing respectively with structural, functional and evolutionary aspects of septins from different organisms: humans, a helminth, a cephalochordate and an alga. In structural terms we propose visualizing directly filaments and proto-filaments using electron microscopy as well as resolving crystal and NMR structures of individual septins and their hetero-complexes, and individual domains in the presence of ligands such as GTP, GDP and Mg2+. These results will be complemented by functional studies which aim to identify, for example, binding partners for the unique septins from a green algae and the mechanisms behind the septin-inhibitor induced paralysis of Schistosoma mansoni. (AU)

Scientific publications

(17)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA DO VALE CASTRO, DANIELLE KAROLINE; DE OLIVEIRA DA SILVA, SABRINA MATOS; PEREIRA, HUMBERTO D'MUNIZ; ALVES MACEDO, JOCI NEUBY; LEONARDO, DIEGO ANTONIO; VALADARES, NAPOLEAO FONSECA; KUMAGAI, PATRICIA SUEMY; BRANDAO-NETO, JOSE; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface. IUCRJ, v. 7, n. 3, p. 462-479, MAY 2020. (10/20290-5, 16/19734-2, 16/04658-9, 12/00268-0, 14/15546-1)

LEONARDO CABREJOS, DIEGO ANTONIO; ALEXANDRINO, ANDRE VESSONI; PEREIRA, CAMILA MALVESSI; MENDONCA, DEBORAH CEZAR; PEREIRA, HUMBERTO D'MUNIZ; MARQUES NOVO-MANSUR, MARIA TERESA; GARRATT, RICHARD CHARLES; GOTO, LEANDRO SEIJI. Structural characterization of a pathogenicity-related superoxide dismutase codified by a probably essential gene in Xanthomonas citri subsp. citri. PLoS One, v. 14, n. 1, JAN 7 2019. (14/15546-1)

MENDONCA, DEBORAH C.; GUIMARAES, SAMUEL L.; PEREIRA, HUMBERTO D'MUNIZ; PINTO, ANDRESSA A.; DE FARIAS, MARCELO A.; DE GODOY, ANDRE S.; ARAUJO, ANA P. U.; VAN HEEL, MARIN; PORTUGAL, V, RODRIGO; GARRATT, RICHARD C.. An atomic model for the human septin hexamer by cryo-EM. Journal of Molecular Biology, v. 433, n. 15, JUL 23 2021. (17/15340-2, 18/20209-5, 18/20816-9, 14/15546-1)

MENDONCA, DEBORAH C.; MACEDO, JOCI N.; GUIMARAES, SAMUEL L.; BARROSO DA SILVA, FERNANDO L.; CASSAGO, ALEXANDRE; GARRATT, RICHARD C.; PORTUGAL, RODRIGO V.; ARAUJO, ANA P. U.. A revised order of subunits in mammalian septin complexes. CYTOSKELETON, v. 76, n. 9-10, p. 457-466, SEP 2019. (15/16116-3, 14/15546-1, 17/15340-2)

SILVA, RAFAEL MARQUES DA; SALADINO, GIOVANNA CHRISTE DOS REIS; LEONARDO, DIEGO ANTONIO; PEREIRA, HUMBERTO D'MUNIZ; ARAUJO, ANA PAULA ULIAN; GARRATT, RICHARD CHARLES. A key piece of the puzzle: The central tetramer of the Saccharomyces cerevisiae septin protofilament and its implications for self-assembly. Journal of Structural Biology, v. 215, n. 3, p. 13-pg., 2023-06-16. (21/08158-9, 20/02897-1, 22/00125-7, 14/15546-1, 18/09687-2)

CASTRO, DANIELLE K. S. V.; ROSA, HIGOR V. D.; MENDONC, DEBORAH C.; CAVINI, ITALO A.; ARAUJO, ANA P. U.; GARRATT, RICHARD C.. Dissecting the Binding Interface of the Septin Polymerization Enhancer Borg BD3. Journal of Molecular Biology, v. 435, n. 13, p. 16-pg., 2023-05-10. (14/15546-1, 18/20209-5, 18/19992-7, 20/02897-1)

BROGNARA, GABRIEL; PEREIRA, HUMBERTO D'MUNIZ; BRANDAO-NETO, JOSE; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. Revisiting SEPT7 and the slippage of beta-strands in the septin family. Journal of Structural Biology, v. 207, n. 1, p. 67-73, JUL 1 2019. (14/15546-1)

KUMAGAI, PATRICIA S.; MARTINS, CARLA S.; SALES, ELISA M.; ROSA, HIGOR V. D.; MENDONCA, DEBORAH C.; DAMALIO, JULIO CESAR P.; SPINOZZI, FRANCESCO; ITRI, ROSANGELA; ARAUJO, ANA PAULA U.. Correct partner makes the difference: Septin G-interface plays a critical role in amyloid formation. International Journal of Biological Macromolecules, v. 133, p. 428-435, JUL 15 2019. (14/15546-1, 17/07709-6)

DIAS ROSA, HIGOR VINICIUS; LEONARDO, DIEGO ANTONIO; BROGNARA, GABRIEL; BRANDAO-NETO, JOSE; PEREIRA, HUMBERTO D'MUNIZ; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. Molecular Recognition at Septin Interfaces: The Switches Hold the Key. Journal of Molecular Biology, v. 432, n. 21, SI, p. 5784-5801, OCT 2 2020. (16/04658-9, 14/15546-1)

LEONARDO, DIEGO A.; CAVINI, ITALO A.; SALA, FERNANDA A.; MENDONCA, DEBORAH C.; ROSA, HIGOR V. D.; KUMAGAI, PATRICIA S.; CRUSCA JR, EDSON; VALADARES, NAPOLEAO F.; MARQUES, IVO A.; BRANDAO-NETO, JOSE; et al. Orientational Ambiguity in Septin Coiled Coils and its Structural Basis. Journal of Molecular Biology, v. 433, n. 9, APR 30 2021. (18/20209-5, 16/04658-9, 17/07709-6, 19/22000-9, 14/15546-1, 15/00062-1, 13/04433-9, 15/16811-3, 18/19992-7)

ZUVANOV, LUIZA; DUARTE MOTA, DIOGO MACIEL; ARAUJO, ANA P. U.; DEMARCO, RICARDO. A blueprint of septin expression in human tissues. FUNCTIONAL & INTEGRATIVE GENOMICS, v. 19, n. 5, p. 787-797, SEP 2019. (14/15546-1)

ZERAIK, ANA ELIZA; STAYKOVA, MARGARITA; FONTES, MARINA GABRIEL; NEMURAITE, INDRE; QUINLAN, ROY; ULIAN ARAUJO, ANA PAULA; DEMARCO, RICARDO. Biophysical dissection of schistosome septins: Insights into oligomerization and membrane binding. Biochimie, v. 131, p. 96-105, DEC 2016. (14/15546-1, 13/20715-4)

PINTO, ANDRESSA P. A.; PEREIRA, HUMBERTO M.; ZERAIK, ANA E.; CIOL, HELOISA; FERREIRA, FREDERICO M.; BRANDAO-NETO, JOSE; DEMARCO, RICARDO; NAVARRO, MARCOS V. A. S.; RISI, CRISTINA; GALKIN, VITOLD E.; et al. Filaments and fingers: Novel structural aspects of the single septin from Chlamydomonas reinhardtii. Journal of Biological Chemistry, v. 292, n. 26, p. 10899-10911, JUN 30 2017. (11/10152-7, 14/15546-1, 12/21259-0, 12/14223-9, 13/20715-4)

FERNANDES, ADRIANO DE FREITAS; LEONARDO, DIEGO ANTONIO; CAVINI, ITALO AUGUSTO; ROSA, HIGOR VINICIUS DIAS; VARGAS, JHON ANTONI; PEREIRA, HUMBERTO D'MUNIZ; NASCIMENTO, ALESSANDRO S.; GARRATT, RICHARD CHARLES. Conservation and divergence of the G-interfaces of Drosophila melanogaster septins. CYTOSKELETON, v. N/A, p. 16-pg., 2023-01-03. (14/15546-1, 19/22000-9, 20/03983-9, 17/18173-0, 20/02897-1, 18/19992-7, 21/08158-9)

DIAS ROSA, HIGOR VINICIUS; LEONARDO, DIEGO ANTONIO; BROGNARA, GABRIEL; BRANDAO-NETO, JOSE; PEREIRA, HUMBERTO D'MUNIZ; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. Molecular Recognition at Septin Interfaces: The Switches Hold the Key. Journal of Molecular Biology, v. 432, n. 21, p. 18-pg., 2020-10-02. (14/15546-1, 16/04658-9)

CAVINI, ITALO A.; LEONARDO, DIEGO A.; ROSA, HIGOR V. D.; CASTRO, DANIELLE K. S. V.; D'MUNIZ PEREIRA, HUMBERTO; VALADARES, NAPOLEAO F.; ARAUJO, ANA P. U.; GARRATT, RICHARD C.. The Structural Biology of Septins and Their Filaments: An Update. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 9, NOV 19 2021. (14/15546-1, 18/19992-7, 20/02897-1, 16/04658-9, 19/22000-9)

SILVA DO VALE CASTRO, DANIELLE KAROLINE; DE OLIVEIRA DA SILVA, SABRINA MATOS; PEREIRA, HUMBERTO D'MUNIZ; ALVES MACEDO, JOCI NEUBY; LEONARDO, DIEGO ANTONIO; VALADARES, NAPOLEAO FONSECA; KUMAGAI, PATRICIA SUEMY; BRANDAO-NETO, JOSE; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface. IUCRJ, v. 7, p. 18-pg., 2020-05-01. (16/04658-9, 16/19734-2, 14/15546-1, 10/20290-5, 12/00268-0)