| Full text | |
| Author(s): |
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
Total Authors: 8
|
| Document type: | Journal article |
| Source: | CYTOSKELETON; v. N/A, p. 16-pg., 2023-01-03. |
| Abstract | |
Septins possess a conserved guanine nucleotide-binding (G) domain that participates in the stabilization of organized hetero-oligomeric complexes which assemble into filaments, rings and network-like structures. The fruit fly, Drosophila melanogaster, has five such septin genes encoding Sep1, Sep2, Sep4, Sep5 and Pnut. Here, we report the crystal structure of the heterodimer formed between the G-domains of Sep1 and Sep2, the first from an insect to be described to date. A G-interface stabilizes the dimer (in agreement with the expected arrangement for the Drosophila hexameric particle) and this bears significant resemblance to its human counterparts, even down to the level of individual amino acid interactions. On the other hand, a model for the G-interface formed between the two copies of Pnut which occupy the centre of the hexamer, shows important structural differences, including the loss of a highly favourable bifurcated salt-bridge network. Whereas wild-type Pnut purifies as a monomer, the reintroduction of the salt-bridge network results in stabilizing the dimeric interface in solution as shown by size exclusion chromatography and thermal stability measurements. Adaptive steered molecular dynamics reveals an unzipping mechanism for dimer dissociation which initiates at a point of electrostatic repulsion within the switch II region. Overall, the data contribute to a better understanding of the molecular interactions involved in septin assembly/disassembly. (AU) | |
| FAPESP's process: | 14/15546-1 - Septins: comparative studies and the correlation between structure and function |
| Grantee: | Richard Charles Garratt |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 19/22000-9 - Septins and flaviviral proteases: a structural analysis |
| Grantee: | Higor Vinícius Dias Rosa |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 20/03983-9 - Structural investigation of ramnose synthesis and implications in antibiotic resistance |
| Grantee: | Alessandro Silva Nascimento |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/18173-0 - Mechanisms Involved in Resistance to Antibiotics: Wall Teichoic Acids and Biofilms as Molecular Targets |
| Grantee: | Alessandro Silva Nascimento |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 20/02897-1 - Septin filaments: structure, polymerization and role in pathologies |
| Grantee: | Richard Charles Garratt |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/19992-7 - Structural studies of septin heteromeric coiled-coils by nuclear magnetic resonance spectroscopy |
| Grantee: | Italo Augusto Cavini |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 21/08158-9 - Crystallographic studies of septins, their individual domains and their complexes |
| Grantee: | Diego Antonio Leonardo Cabrejos |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |