Fig. 2

Examples of co-operative interactions mediated by DNA, RNA and protein motifs. a DNA motif specificity through multivalent interactions with motif-binding domains in multimeric complexes. Structure of Retinoic acid receptor alpha (RARA) (green) and Retinoic acid receptor RXR-alpha (RXRA) (red) heterodimer bound to a retinoic acid response element (5′-AGGTCAAAGGTCA-3′) (blue) [107]. Each protein binds to a 6-mer “half-site” (5′-AGGTCA-3′) giving the complex specificity for a 12-mer motif. b RNA motif specificity through multivalent interactions with tandem arrays of motif-binding domains. Structure of the tandem Zinc Fingers of Zinc finger protein 36, C3H1 type-like 2 (ZFP36L2) (green) bound to an RNA class II AU-rich element (ARE) (5′-UUAUUUAUU-3′) (blue). Each Zinc Finger recognises 4 nucleotides of RNA, allowing the tandem domains to recognise an 8-mer motif [78]. c Protein motif specificity through multivalency. Structure of yeast APC/C-Cdh1 modulator 1 (Acm1) (blue) bound to APC/C activator protein Cdh1 (green) showing the 3 binding pockets for the D box (RxxLxxL), KEN box (KEN) and ABBA motif (FxLYxE) on the WD40 repeat of Cdh1 [80]. d Example of competitive motif-mediated binding involving two motifs. Binding of a single biomolecule/complex to a motif is sufficient to perform the biological function; however, when a second biomolecule is present, the function facilitated by the first site is inhibited [19, 87, 148–150]. e Schematic example of co-operative motif-mediated interactions involving two motifs. In the example, binding of a single interface is insufficient to elicit the functional outcome of binding. Once the second motif-binding interface associates, the trimeric complex can bind with sufficient affinity/avidity to elicit the biological outcome. f Modification on or near a regulatory motif can modulate the motif either positively [89, 151–154] or negatively [18, 19, 94]. g Motif accessibility is required for binding partner recruitment and, consequently, is often utilised as a step of regulation [18, 19, 99, 100, 155]