Work

Calpain small subunit homodimerization is robust and calcium‐independent

Year: 2026

Type: article

Abstract: Calpains dimerize via penta‐EF‐hand (PEF) domains, but their mechanical stability and kinetics remain incompletely characterized. Here, we used single‐molecule force spectroscopy on an EGFP‐tagged calpain small subunit PEF (CAPNS1‐PEF) homodimer to quantify dissociation mechanics. Across retraction speeds of 0.2–10 μm/s, homodimer rupture required large forces (> 300 pN). Rupture forces and force‐induced unfolding did not change when Ca 2+ was removed, suggesting Ca 2+ ‐independent mechanics, consistent with crystal structures showing minimal Ca 2+ ‐induced conformational changes in the PEF domain. Together, these results indicate that EF‐hands in the CAPNS1 homodimer function primarily as structural elements within a mechanically robust, Ca 2+ ‐insensitive dimerization scaffold.

Source: FEBS Letters

DOI: 10.1002/1873-3468.70321

Authors: Nesha May O. Andoy, Trina Dykstra‐MacPherson, Mathias A. Bell, Peter L. Davies, Ruby May A. Sullan

Institutions: University of Toronto Scarborough, Queen's University, University of Toronto

Language: English

Topic: Calpain Protease Function and Regulation

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,980

Funder: Natural Sciences and Engineering Research Council of Canada