Interaction of DTX3L/PARP9 and ADP-ribosylated
AR peptides measured
by FP assays. (a) Oligomerization of DTX3L/PARP9 is critical for recognition
of a dual ADP-ribosylated AR peptide. (b) DTX3L/PARP9 binding competes
with ADP-ribose (50 μM) in solution. Assays were performed in
triplicate in a 384-well plate (Corning 3575) containing 50 nM fluorescently
labeled AR peptide and recombinant proteins [final concentration 2500
nM in (a) or 2000 nM in (b), and 2-fold serial dilution] in a binding
buffer (20 mM Tris–HCl, pH 7.5, 50 mM NaCl, 0.1 mM EDTA, and
2 mM DTT). The reaction mixture was incubated at RT for 45 min, FP
measured in a PHERAstar FSX Microplate Reader (BMG Labtech), and the
binding curves were fitted for specific binding with GraphPad Prism
v 9.3.1. The error bars represent the standard deviations. Dual-ADPr
peptide 1: CF-RPTPC(ADPr)APLAEC(ADPr)KGSL–OH;
mono-ADPr peptides 2: CF-PLAEC(ADPr)KGSL–OH; 3: CF-RPTPC(ADPr)APLA–OH; 4: CF-RPTCAPLAEC(ADPr)KGSL–OH; 5: CF-RPTPC(ADPr)APLAECKGSL–OH. Control non-ADP-ribosylated
peptide 6: CF-RPTPCAPLAECKGSL–OH. Recombinant
proteins were checked by SDS-PAGE as seen in Figure S10.