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. 2026 Feb 6;12(6):eadz3483. doi: 10.1126/sciadv.adz3483

Fig. 3. Importance of structural context and exposure of degrons.

Fig. 3.

(A) Kernel density estimate (KDE) plot correlating the average rASA of each tile with its degron score. Dark green indicates high density. (B) KDE plot of the average pLDDT of each tile with its degron score. Dark red indicates high density. KDE was computed with bandwidth of 0.1316. (C) Correlation of average degron score of all tiles of a protein with its protein stability index (PSI) as determined in (12). The correlation is shown only for 173 proteins with the highest average exposure (rASA > 0.7) (D) Representative FC profile of full-length KRTAP11-1 containing several exposed degrons with BZ (15 μM, for 16 hours) or without (DMSO) treatment (KRTAP11-1, n = 1887; and KRTAP11-1 and BZ, n = 1234). The GFP:mCherry profile of the empty vector (EV) control is shown for comparison (n = 1730). (E) Representative FC profiles of LAP3 and RAB6C with BZ (15 μM, for 16 hours) or without (DMSO) treatment and with degron deleted (Δdegron) or wild type (WT). (LAP3 WT, n = 10,087; LAP3 WT and BZ, n = 7122; LAP3 DD, n = 7177; LAP3 DD and BZ, n = 6548; RAB6C WT, n = 7499; RAB6C WT and BZ, n = 5942; RAB6C DD, n = 7700; and RAB6C DD and BZ, n = 5955). The AlphaFold predicted structures of LAP3 (AF-P28838-F1) and RAB6C (AF-Q9H0N0-F1) are shown on the right with the deleted degrons marked in red. The degron scores of the deleted degrons (shown in red) were as follows: LAP3 tile 1: degron score of 1 and average tile rASA of 0.93. RAB6C tile 15: degron score of 0.7 and average tile rASA of 0.86. All FC experiments were performed in duplicate.