Novel lipid-interaction motifs within the C-terminal domain of Septin10 from Schistosoma mansoni

DOI: 10.1016/j.bbamem.2024.184371

Authors: Italo A. Cavini (University of São Paulo) , Marina G. Fontes (University of São Paulo) , Ana Eliza Zeraik (North Fluminense State University Darcy Ribeiro) , Jose L. S. Lopes (University of São Paulo) , Ana Paula U. Araujo (University of São Paulo)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochimica Et Biophysica Acta (bba) - Biomembranes , VOL 1866

State: Published (Approved)
Published: October 2024
Diamond Proposal Number(s): 33825

Abstract: Septins are cytoskeletal proteins and their interaction with membranes is crucial for their role in various cellular processes. Septins have polybasic regions (PB1 and PB2) which are important for lipid interaction. Earlier, we and others have highlighted the role of the septin C-terminal domain (CTD) to membrane interaction. However, detailed information on residues/group of residues important for such feature is lacking. In this study, we investigate the lipid-binding profile of Schistosoma mansoni Septin10 (SmSEPT10) using PIP strip and Langmuir monolayer adsorption assays. Our findings highlight the CTD as the primary domain responsible for lipid interaction in SmSEPT10, showing binding to phosphatidylinositol phosphates. SmSEPT10 CTD contains a conserved polybasic region (PB3) present in both animals and fungi septins, and a Lys (K367) within its putative amphipathic helix (AH) that we demonstrate as important for lipid binding. PB3 deletion or mutation of this Lys (K367A) strongly impairs lipid interaction. Remarkably, we observe that the AH within a construct lacking the final 43 amino acid residues is insufficient for lipid binding. Furthermore, we investigate the homocomplex formed by SmSEPT10 CTD in solution by cross-linking experiments, CD spectroscopy, SEC-MALS and SEC-SAXS. Taken together, our studies define the lipid-binding region in SmSEPT10 and offer insights into the molecular basis of septin-membrane binding. This information is particularly relevant for less-studied non-human septins, such as SmSEPT10.

Diamond Keywords: Schistosomiasis

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS

Added On: 22/07/2024 09:44

Discipline Tags:

Pathogens Infectious Diseases Disease in the Developing World Health & Wellbeing Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech Parasitology

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)