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J. Chamot-Rooke

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Open access Jul 2026

Core–sheath coupling controls flagellar curvature and motility in Leptospira

Spirochaete pathogens are among the most invasive bacteria known, causing syphilis, Lyme disease, and leptospirosis. Their tissue penetration depends on periplasmic flagellar filaments that, unlike other bacterial flagella, are encased in a spirochaete-specific multi-protein sheath and deform the cell body into motile waves. How these filaments achieve the mechanical properties needed for invasive motility has remained unclear. Here we determine complete atomic structures of the Leptospira endoflagellar filament, revealing an elaborate sheath of 9 to 12 distinct asymmetrically arranged proteins. We show that the flagellin variant forming the filament core determines sheath composition, producing curvatures ranging from ~3.5 µm−1 to ~5.6 µm−1. The lower-curvature architecture, employed by pathogenic Leptospira interrogans, proves essential for motility in viscous environments and during infection. Thus, Leptospira achieves environment-specific motility through modular core–sheath coupling, linking atomic-scale structural plasticity to large-scale changes in swimming behaviour. Conservation of key sheath components suggests this mechanism may extend across spirochaetes. Pathogenic spirochaetes have periplasmic flagella that give these bacteria their spiral shape and enable penetration into host tissues. Here, San Martin et al. present detailed structures of the flagellar filaments and their multi-protein sheath, linking structural plasticity to motility changes.

Fabiana San Martin, M. R. Brady, L. Fule et al. · 1 citation
Review Open access Sep 2026

Proteoforms in Disease: Biomedical Applications of Top-Down Proteomics.

The proteome is a dynamic landscape of proteoforms arising from genetic mutations, alternative splicing, and post-translational modifications (PTMs), which collectively drive biological function and disease phenotypes. Mass spectrometry (MS)-based proteomics has emerged as an essential technique for elucidating this molecular complexity. Although bottom-up proteomics enables deep protein identification and quantification through peptide-level analysis, it disrupts molecular connectivity and introduces a peptide-to-protein inference problem, which is suboptimal for proteoform analysis. Top-down proteomics (TDP) offers a complementary approach by analyzing intact proteins, preserving molecular connectivity, and enabling direct characterization and quantification of proteoforms. This capability is increasingly vital for understanding heterogeneous human diseases. Here, we review the evolving role of TDP in biomedical research, highlighting studies that revealed proteoform-level alterations, identified candidate biomarkers, and advanced our understanding of the roles of proteoforms in human diseases.

Holden T. Rogers, Zachery R. Gregorich, Megan S. Gant et al. · 0 citations

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