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. Author manuscript; available in PMC: 2019 Mar 22.
Published in final edited form as: Cell. 2018 Mar 8;173(1):62–73.e9. doi: 10.1016/j.cell.2018.02.026

Figure 7. Analysis of the IAPP oligomer toxicity-rescuing ability of 111 ZMPSTE24 missense mutants.

Figure 7

ZMPSTE24 mutants identified from the sequencing of diabetes patients and healthy controls were tested for their ability to rescue 6xIAPP toxicity in the Δste24 yeast strain. The growth of 6xIAPP strains expressing ZMPSTE24 variants was quantified as the area under the growth curve at 48 hours. A) Each cell of the heat map is the average growth of four biological replicates, while each column is a technical replicate. B) Retest of poorly growing variants. Variants meeting statistical significance were deemed loss-of-function variants (One-sided ANOVA followed by Dunnett’s test, cutoff: p < 0.01) and are shown in blue bars. Error bars = SD. C) Residues in ZMPSTE24 where amino acid changes produced lower 6xIAPP toxicity rescuing activity are shown on the crystal structure (PDB: 5SYT) in orange, with laminopathy-causing variants shown in red.