Izumi, C. | Search bioRxiv

bioRxiv2026

Structural modelling and biophysical analyses reveal a dimeric coiled-coil architecture in the FAZ10 central region of Trypanosoma brucei

Trypanosoma brucei relies on the flagellum attachment zone (FAZ) to coordinate flagellum positioning, cell morphology, and cytokinesis. The giant FAZ10 protein, which contains both repetitive and structured regions, is essential for correct cleavage-furrow placement, yet its molecular organization remains unresolved due to its exceptional size. In this study, we define the architecture of the FAZ10 central region through structural modelling and biophysical validation. AlphaFold2 and molecular dynamics simulations defined a parallel coiled-coil dimer flanked by symmetric globular domains, with canonical hydrophobic core packing, complementary interhelical contacts, and local heptad discontinuities, including a stammer-stutter pair that modulates the superhelical geometry. Biophysical analyses show that this region forms a stable dimer in solution, mediated by the coiled-coil domain and consistent with a predominantly -helical structure. Together, these findings identify the FAZ10 central region as a semi-flexible dimeric scaffold that provides a structural framework for understanding FAZ supramolecular organization and the integration of large cytoskeletal assemblies in trypanosomatids.

biophysics↗

bioRxiv2025

The Renin-Angiotensin System Modulates SARS-CoV-2 Entry via ACE2 Receptor

The RAS plays a central role in cardiovascular regulation and has gained prominence in the pathogenesis of COVID-19 due to the critical function of ACE2 as the entry receptor for SARS-CoV-2. Angiotensin IV, but not angiotensin II, has recently been reported to enhance the binding between the viral spike protein and ACE2. To investigate the virological significance of this effect, we developed a single-round infection assay using SARS-CoV-2 viral-like particles expressing the spike protein. Our results demonstrate that while angiotensin II does not affect viral infectivity across concentrations ranging from 40LnM to 400LnM, angiotensin IV enhances viral entry at a low concentration but exhibits dose-dependent inhibition at higher concentrations. These findings highlight the unique dual role of angiotensin IV in modulating SARS-CoV-2 entry. In silico molecular docking simulations indicate that angiotensin IV was predicted to associate with the S1 domain near the receptor-binding domain in the open spike conformation. Given that reported plasma concentrations of angiotensin IV range widely from 17 pM to 81 nM, these levels may be sufficient to promote, rather than inhibit, SARS-CoV-2 infection. This study identifies a novel link between RAS-derived peptides and SARS-CoV-2 infectivity, offering new insights into COVID-19 pathophysiology and informing potential therapeutic strategies.

microbiology↗