Fig. 4: Properties of P53 DBD and Lamin A/C IgD variants. | Genetics in Medicine

Fig. 4: Properties of P53 DBD and Lamin A/C IgD variants.

From: A rapid solubility assay of protein domain misfolding for pathogenicity assessment of rare DNA sequence variants

Fig. 4: Properties of P53 DBD and Lamin A/C IgD variants.The alternative text for this image may have been generated using AI.

(a) Structure of the P53 DBD (PDB: 1TSR) with cancer-associated variants in green. (b) Representative immunoblots of recombinant DBD variants expressed in E. coli. Bars ± SD represent relative solubility (% of wild type [WT]) determined by dot blot (n ≥ 3). Reported ΔΔG values are shown below for comparison.18,19,20 (c) Structure of the Lamin A/C IgD (PDB: 1IFR) with variants color-coded based on disease. (d) Representative immunoblots of recombinant IgD variants expressed in E. coli. Bars ± SD represent relative solubility (% of WT) determined by dot blot. (e) 40× images of HEK nuclei after GFP-tagged full-length Lamin A variant overexpression. (f) Bars ± SD represent the percentage of cells showing aggregation for each variant (n ≥ 4 transfections). Disease classifications from Universal Mutation Database (UMD). *P < 0.05, a significant reduction in solubility of variants compared with WT (b,d) or significant increase in aggregation (f). 1A–2B coiled-coil “rod” domains, DBD DNA-binding domain, IgD Immunoglobulin-like domain, n/a not available, OD oligomerization domain, PRD proline rich domain, RegD C-term regulatory domain, TAD transactivation domain.

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