7AHO

RUVBL1-RUVBL2 heterohexameric ring after binding of RNA helicase DHX34

Summary for 7AHO

• Entry DOI: 10.2210/pdb7aho/pdb
• EMDB information: 11788 11789
• Descriptor: RuvB-like 1, RuvB-like 2, ADENOSINE-5'-DIPHOSPHATE (3 entities in total)
• Functional Keywords: ruvbl1-ruvbl2, dhx34, nonsense-mediated mrna decay, rna degradation, cryo-em, translation
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 318555.28

Authors

Lopez-Perrote, A.,Rodriguez, C.F.,Llorca, O. (deposition date: 2020-09-25, release date: 2020-11-25, Last modification date: 2025-10-01)

Primary citation

Lopez-Perrote, A.,Hug, N.,Gonzalez-Corpas, A.,Rodriguez, C.F.,Serna, M.,Garcia-Martin, C.,Boskovic, J.,Fernandez-Leiro, R.,Caceres, J.F.,Llorca, O.
Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.
Elife, 9:-, 2020

PubMed Abstract: Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1, and R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity is required for NMD activation by an unknown mechanism. Here, we show that DHX34, an RNA helicase regulating NMD initiation, directly interacts with RUVBL1-RUVBL2 in vitro and in cells. Cryo-EM reveals that DHX34 induces extensive changes in the N-termini of every RUVBL2 subunit in the complex, stabilizing a conformation that does not bind nucleotide and thereby down-regulates ATP hydrolysis of the complex. Using ATPase-deficient mutants, we find that DHX34 acts exclusively on the RUVBL2 subunits. We propose a model, where DHX34 acts to couple RUVBL1-RUVBL2 ATPase activity to the assembly of factors required to initiate the NMD response.

PubMed: 33205750
DOI: 10.7554/eLife.63042

Experimental method

ELECTRON MICROSCOPY (4.18 Å)