Fig. 5: Activator binding and mapping of disease mutations in TRRAP.
a, Surface representation of TRRAP colored by domains. Mapped activator-binding regions are indicated as colored overlays. The c-Myc binding region is probably located in a disordered loop between two helices. Boxes indicate the relative views in the following panels. b, Surface representation colored by conservation (for details, see Extended Data Fig. 6c). c,d Residue mutations associated with cancer, autism, or intellectual disability34,37. c, Most disease mutations lie in a region of high sequence conservation. Surface coloring as in b. d, Surface representation of disease mutations as shown in a. Red, surface exposed, probably interfere with activator binding; orange, buried, likely to structurally destabilize TRRAP (Extended Data Fig. 10a,b) or the interaction with SUPT20H (e,f). e, A disease-causing mutation of F859 is located at the interface with the SUPT20H CTD. f, R3746 forms a salt bridge with D291 of the SUPT20H latch. The disease mutation R3746Q disrupts the salt bridge. The reported residue numbers relate to the modeled isoform (Uniprot F2Z2U4).
