7OGG

Nse5/6 complex

Summary for 7OGG

• Entry DOI: 10.2210/pdb7ogg/pdb
• Descriptor: Non-structural maintenance of chromosome element 5,Non-structural maintenance of chromosome element 5,Non-structural maintenance of chromosome element 5, DNA repair protein KRE29,DNA repair protein KRE29,DNA repair protein KRE29 (2 entities in total)
• Functional Keywords: nse5/6, dna binding protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 105127.79

Authors

Basquin, J.,Taschner, M.,Gruber, S. (deposition date: 2021-05-06, release date: 2021-07-07, Last modification date: 2024-11-13)

Primary citation

Taschner, M.,Basquin, J.,Steigenberger, B.,Schafer, I.B.,Soh, Y.M.,Basquin, C.,Lorentzen, E.,Raschle, M.,Scheltema, R.A.,Gruber, S.
Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding.
Embo J., 40:e107807-e107807, 2021

PubMed Abstract: Eukaryotic cells employ three SMC (structural maintenance of chromosomes) complexes to control DNA folding and topology. The Smc5/6 complex plays roles in DNA repair and in preventing the accumulation of deleterious DNA junctions. To elucidate how specific features of Smc5/6 govern these functions, we reconstituted the yeast holo-complex. We found that the Nse5/6 sub-complex strongly inhibited the Smc5/6 ATPase by preventing productive ATP binding. This inhibition was relieved by plasmid DNA binding but not by short linear DNA, while opposing effects were observed without Nse5/6. We uncovered two binding sites for Nse5/6 on Smc5/6, based on an Nse5/6 crystal structure and cross-linking mass spectrometry data. One binding site is located at the Smc5/6 arms and one at the heads, the latter likely exerting inhibitory effects on ATP hydrolysis. Cysteine cross-linking demonstrated that the interaction with Nse5/6 anchored the ATPase domains in a non-productive state, which was destabilized by ATP and DNA. Under similar conditions, the Nse4/3/1 module detached from the ATPase. Altogether, we show how DNA substrate selection is modulated by direct inhibition of the Smc5/6 ATPase by Nse5/6.

PubMed: 34191293
DOI: 10.15252/embj.2021107807

Experimental method

X-RAY DIFFRACTION (3.29 Å)