The tail domain of lamin B1 is more strongly modulated by divalent cations than lamin A.

The nucleoskeleton contains mainly nuclear intermediate filaments made of lamin proteins. Lamins provide nuclear structure and also play a role in various nuclear processes including signal transduction, transcription regulation and chromatin organization. The disparate functions of lamins may be related to the intrinsic disorder of the tail domains, which allows for altered and promiscuous binding. Here, we show modulation of lamin tail domain structures in the presence of divalent cations. We utilize changes in fluorescence of tryptophan residues within the Ig-fold flanked by disordered regions to experimentally measure protein thermodynamics. Using spectroscopy experiments and molecular dynamics simulations, we show that the tail domain of lamin B1 shows enhanced association with both Ca(2+) and Mg(2+) compared to the tail domain of lamin A. Binding curves show a similar KD between protein and ion (250-300 μM) for both proteins with both ions. However, we observe a maximum binding of ions to lamin B1 tail domain which is 2-3 times greater than that for lamin A tail domain by both experiment and simulation. Using simulations, we show that divalent ion association alters the Ig-fold by pinning flanking regions. With cells in culture, we observe altered lamin B1 organization in the presence of excess Mg(2+) more so than for lamin A. We suggest that the differential sensitivity to divalent cations contributes to the vastly different functionalities and binding of the 2 proteins.