8FTK

Chaetomium thermophilum SETX (Full-length)

Summary for 8FTK

• Entry DOI: 10.2210/pdb8ftk/pdb
• Related: 8FTM
• EMDB information: 29426 29439 29440
• Descriptor: 5'-3' RNA helicase-like protein (1 entity in total)
• Functional Keywords: helicase, transcription, dna repair, rna-dna hybrid
• Biological source: Thermochaetoides thermophila DSM 1495
• Total number of polymer chains: 1
• Total formula weight: 223790.11

Authors

Williams, R.S.,Appel, C.D. (deposition date: 2023-01-12, release date: 2023-10-25, Last modification date: 2023-11-01)

Primary citation

Appel, C.D.,Bermek, O.,Dandey, V.P.,Wood, M.,Viverette, E.,Williams, J.G.,Bouvette, J.,Riccio, A.A.,Krahn, J.M.,Borgnia, M.J.,Williams, R.S.
Sen1 architecture: RNA-DNA hybrid resolution, autoregulation, and insights into SETX inactivation in AOA2.
Mol.Cell, 83:3692-, 2023

PubMed Abstract: The senataxin (SETX, Sen1 in yeasts) RNA-DNA hybrid resolving helicase regulates multiple nuclear transactions, including DNA replication, transcription, and DNA repair, but the molecular basis for Sen1 activities is ill defined. Here, Sen1 cryoelectron microscopy (cryo-EM) reconstructions reveal an elongated inchworm-like architecture. Sen1 is composed of an amino terminal helical repeat Sen1 N-terminal (Sen1N) regulatory domain that is flexibly linked to its C-terminal SF1B helicase motor core (Sen1) via an intrinsically disordered tether. In an autoinhibited state, the Sen1 domain regulates substrate engagement by promoting occlusion of the RNA substrate-binding cleft. The X-ray structure of an activated Sen1 engaging single-stranded RNA and ADP-SO shows that the enzyme encircles RNA and implicates a single-nucleotide power stroke in the Sen1 RNA translocation mechanism. Together, our data unveil dynamic protein-protein and protein-RNA interfaces underpinning helicase regulation and inactivation of human SETX activity by RNA-binding-deficient mutants in ataxia with oculomotor apraxia 2 neurodegenerative disease.

PubMed: 37832548
DOI: 10.1016/j.molcel.2023.09.024

Experimental method

ELECTRON MICROSCOPY (4.56 Å)