title: Structure of active dimeric human telomerase.
abstract: Telomerase contains a large RNA subunit, TER, and a protein catalytic subunit, TERT. Whether telomerase functions as a monomer or dimer has been a matter of debate. Here we report biochemical and labeling data that show that in vivo-assembled human telomerase contains two TERT subunits and binds two telomeric DNA substrates. Notably, catalytic activity requires both TERT active sites to be functional, which demonstrates that human telomerase functions as a dimer. We also present the three-dimensional structure of the active full-length human telomerase dimer, determined by single-particle EM in negative stain. Telomerase has a bilobal architecture with the two monomers linked by a flexible interface. The monomer reconstruction at 23-Å resolution and fitting of the atomic structure of the TERT subunit from beetle Tribolium castaneum into the EM density reveals the spatial relationship between RNA and protein subunits, providing insights into telomerase architecture.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Anselm
authors.initials: A
authors.lastname: Sauerwald
authors.forename: Sara
authors.initials: S
authors.lastname: Sandin
authors.forename: Gaël
authors.initials: G
authors.lastname: Cristofari
authors.forename: Sjors H W
authors.initials: SH
authors.lastname: Scheres
authors.forename: Joachim
authors.initials: J
authors.lastname: Lingner
authors.forename: Daniela
authors.initials: D
authors.lastname: Rhodes
mesh_terms: D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D011487:Protein Conformation; D013379:Substrate Specificity; D019098:Telomerase / Q000737:chemistry*
chemical_list: D019098:Telomerase