Fig. 3: Zipper head residue Leu980 in TERT limits the length of the primer–template duplex.
From: Zipper head mechanism of telomere synthesis by human telomerase
a Left, structure of the catalytic core of human telomerase as colored in Fig. 1, with the active cavity of TERT highlighted in dashed red box. Right, close-up view of the primer–template duplex in the active site of TERT. The catalytic center of telomerase is defined as ‘position 1’ which is vacant in the EM structure. The zipper head residue Leu980 in the thumb helix of TERT is shown in stick model. b Schematic diagram of the primer–template duplex in the structure in which the zipper head Leu980 (light green circle) destabilizes and disrupts the canonical W-C hydrogen pairing at positions 5 and positions 6 and 7. c Details of the base pairing of the primer–template duplex at the AGGG 3′-end of the DNA substrate. The wobble pair dA5–U53 at position 5 no longer mediates canonical W-C hydrogen bonding interactions due to the disruptive effect of Leu980. d MD simulation scatter plots of the geometrical base pair descriptors of the RNA–DNA hybrid at positions 4 and 5 in WT and L980G mutant TERT proteins, respectively. e Position on the thumb helix equivalent to human TERTLeu980 is occupied by an invariant glycine residue (cyan ball) in canonical protein-only RTs.
