Fig. 5.
Models of structural heterogeneity in human shelterin. (A) Visual depiction of conformational variability within POT1/TPP1N. In these models, the C-terminal domains of POT1 are arbitrarily used as an anchor. Conformational variability of the DNA-binding OB folds and the TPP1 OB fold is depicted as an ensemble of possible conformations that these features can adopt relative to that anchor. (B) Models for flexibility within POT1/TPP1/TIN2. The TRFH domain of TIN2 is shown occupying different discrete positions on the POT1 anchor. For the “toy snake” model, structured domains are depicted as hexagonal snake segments with flexible linkers shown as dotted lines connecting them. These domains can associate with each other in a variety of conformations, and truncation of flexible linkers would result in only minor changes in structure and conformational variability. (C) Model for structural heterogeneity of the TRF1 complex. The POT1/TPP1/TIN2 subcomplex remains flexible and TIN2 is presumably flexibly tethered to TRF1.