Fig. 5: Structural basis for penultimate residue tolerance amongst KLHDC10 degrons.
From: Structural basis for C-degron selectivity across KLHDCX family E3 ubiquitin ligases
a Close up view of UB (orange) bound to the KLHDC10 (marine) C-degron binding pocket. Modeled conformations of consensus penultimate residues Pro (light orange, sticks) and Trp (yellow orange, sticks) are shown and their structural clash with KLHDC10 F176 is labeled. KLHDC10 residues (I174, L127, A155, and Y110) that form a cryptic hydrophobic pocket behind F176 are shown in sticks. b Surface representation of the KLHDC10 (marine) binding pocket, highlighting the structural clash of KLHDC10 with modeled penultimate residues Pro (light orange, sticks) and Trp (yellow orange, sticks). Hydrophobic surfaces are colored white, positively charged surfaces blue, and negatively charged surfaces red. c Same as (b), but with a F176 flipped rotamer of KLHDC10 revealing a cryptic binding pocket that can accommodate penultimate Pro or Trp from KLHDC10 consensus degrons. d C-terminal sequences of the KLHDC10 degron variants used in surface plasmon resonance and biochemical studies. Equilibrium binding affinities obtained from SPR experiments (Kd) are shown. Values are the average +/− 1 SD from n = 2 independent experiments. e Quantification of pulse-chase ubiquitylation assays monitoring UBE2R2-mediated ubiquitylation of UB or the indicated C-terminal mutations by CRL2KLHDC10. f Same as (e). Bar graphs are the average of n = 2 independent experiments. Source data are provided as a Source Data file.
