( b) Human TNKS2 ARC4 is shown in surface representation with bound TBM peptidesTankyrase Binders from 3BP23BP2 (SH3BP2, SH3 domain-binding protein 2) and MCL1 shown in stick representation with the core TBM octapeptide colored purple and orange, respectively, and by heteroatom.
( b) and ( c) Examples for ARC–TBM interactions studied by X-ray crystallography. ( a) Domain organization of human tankyrase and tankyrase 2 (modified from ). Given four peptide-binding ARCs, tankyrase recognizes its binders multivalentlyMultivalent binding. Out of the five ARCs, the central one (ARC3) is devoid of a known peptide-binding function while the other four (ARCs 1, 2, 4, and 5) each feature a highly Conserved peptide-binding pocket with similar specificities (Fig. TBMs are recognized by tankyrase’s Ankyrin repeat clusters (ARCs). In-silico prediction of Tankyrase binding motifs (TBMs), which in its simplest form consists of six to eight consecutive amino acids. All Tankyrase binders characterized to date bear a tankyrase-binding motif (TBM)Tankyrase binding motif (TBM) The recruitment of tankyraseTankyrase recruitment to differentTankyrase Binders protein complexes associated with specific cellular processes and situated at different subcellular locations defines its diverse functions. The biological roles of the two Tankyrases are largely redundant, pointing to shared molecular mechanisms. Fig.1a), 1a), contributes to both the nuclear and cytoplasmic pools of PAR. The PARP tankyrase, of which there are two human paralogs (TNKS/ARTD5, TNKS2/ARTD6Tankyrase (TNKS/ARTD5, TNKS2/ARTD6), see Fig. PARylation is most commonly associated with nuclear events such as gene regulation and DNA damage repairDNA damage repair, but PAR is found in both the nucleus and the cytoplasm. PAR can thus act as a scaffolding component as well as a regulatory PTM. The resulting long, strongly negatively charged PAR chains provide attachment sites for proteins endowed with PAR-binding modules or directly affect substrate function. Tankyrase Binders enzymes, which serially transfer ADP-ribose from NAD + Poly(ADP-ribosyl)ation (PARylation) constitutes a striking posttranslational modification (PTM) catalyzed by poly(ADP-ribose)polymerase (PARP)Poly(ADP-ribose) polymerases (PARPs)
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