Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure of active human telomerase with telomere shelterin protein TPP1.
Journal, issue, pages	Nature, Vol. 604, Issue 7906, Page 578-583, Year 2022
Publish date	Apr 13, 2022
Authors	Baocheng Liu / Yao He / Yaqiang Wang / He Song / Z Hong Zhou / Juli Feigon /
PubMed Abstract	Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG. Its activity is a determinant of cancer ...Human telomerase is a RNA-protein complex that extends the 3' end of linear chromosomes by synthesizing multiple copies of the telomeric repeat TTAGGG. Its activity is a determinant of cancer progression, stem cell renewal and cellular aging. Telomerase is recruited to telomeres and activated for telomere repeat synthesis by the telomere shelterin protein TPP1. Human telomerase has a bilobal structure with a catalytic core ribonuclear protein and a H and ACA box ribonuclear protein. Here we report cryo-electron microscopy structures of human telomerase catalytic core of telomerase reverse transcriptase (TERT) and telomerase RNA (TER (also known as hTR)), and of telomerase with the shelterin protein TPP1. TPP1 forms a structured interface with the TERT-unique telomerase essential N-terminal domain (TEN) and the telomerase RAP motif (TRAP) that are unique to TERT, and conformational dynamics of TEN-TRAP are damped upon TPP1 binding, defining the requirements for recruitment and activation. The structures further reveal that the elements of TERT and TER that are involved in template and telomeric DNA handling-including the TEN domain and the TRAP-thumb helix channel-are largely structurally homologous to those in Tetrahymena telomerase, and provide unique insights into the mechanism of telomerase activity. The binding site of the telomerase inhibitor BIBR1532 overlaps a critical interaction between the TER pseudoknot and the TERT thumb domain. Numerous mutations leading to telomeropathies are located at the TERT-TER and TEN-TRAP-TPP1 interfaces, highlighting the importance of TER-TERT and TPP1 interactions for telomerase activity, recruitment and as drug targets.
External links	Nature / PubMed:35418675 / PubMed Central
Methods	EM (single particle)
Resolution	3.3 - 4.3 Å
Structure data	26085 7trc EMDB-26085, PDB-7trc: Human telomerase H/ACA RNP at 3.3 Angstrom Method: EM (single particle) / Resolution: 3.3 Å 26086 7trd EMDB-26086, PDB-7trd: Human telomerase catalytic core structure at 3.3 Angstrom Method: EM (single particle) / Resolution: 3.3 Å 26087 7tre EMDB-26087, PDB-7tre: Human telomerase catalytic core with shelterin protein TPP1 Method: EM (single particle) / Resolution: 3.5 Å 26088 7trf EMDB-26088, PDB-7trf: Human telomerase catalytic core RNP with H2A/H2B Method: EM (single particle) / Resolution: 3.7 Å EMDB-26090: Human telomerase catalytic core with TPP1-OB, P2a state1-1 Method: EM (single particle) / Resolution: 4.2 Å EMDB-26091: Human telomerase catalytic core with TPP1-OB, P2a state 1-2 Method: EM (single particle) / Resolution: 4.1 Å EMDB-26092: Human telomerase catalytic core with TPP1-OB, P2a state1-3 Method: EM (single particle) / Resolution: 4.1 Å EMDB-26093: Human telomerase catalytic core with TPP1-OB, P2a state2 Method: EM (single particle) / Resolution: 4.0 Å EMDB-26094: Human telomerase catalytic core without TPP1-OB, P2a state1 Method: EM (single particle) / Resolution: 4.3 Å EMDB-26095: Human telomerase catalytic core without TPP1-OB, P2a state2 Method: EM (single particle) / Resolution: 4.1 Å EMDB-26096: Human telomerase catalytic core without TPP1 Method: EM (single particle) / Resolution: 3.7 Å
Source	homo sapiens (human)
Keywords	REPLICATION / DNA / RNA