The Hansenula Polymorpha Telomerase provides insights into the structure and functions of Est3.
Telomerase, a ribonucleoprotein enzymatic complex, maintains genome integrity and promotes cellular growth in eukaryotes. The telomerase enzyme from the thermotolerant fungus Hansenula Polymorpha contains, in addition the catalytic component (TERT) as well as telomerase-RNA (TER), the accessory proteins Est1 & Est3, both of which are crucial for the in vivo function of telomerase. We report here the high-resolution crystal structure of Est3 (HpEst3) from Hansenula Polymorpha in solution as well as its functional relationships with the other components of the telomerase. HpEst3 has a similar structure to Est3 from Saccharomyces Cervisiae, and human TPP1. In H. polymorpha, telomerase is dependent on both Est3 proteins and Est1 in a functionally-symmetrical way. In the absence of Est3 or Est1, the formation of stable ribonucleoproteins is prevented, the binding of another protein to TER is weakened, and the amount of TERT in the cell decreases, probably due to destabilization of the telomerase RNA. In vitro, NMR probes have shown that free Est3 does not interact directly with either the N-terminal TERT domain or DNA or RNA fragments simulating the likely telomerase environments. Our results confirm the notion that telomerase has the evolutionary variable functionality within a conservative structural context.
Source:
https://www.nature.com/articles/s41598-020-68107-x
