eprintid: 10116858 rev_number: 14 eprint_status: archive userid: 608 dir: disk0/10/11/68/58 datestamp: 2020-12-09 17:12:19 lastmod: 2021-10-09 23:07:29 status_changed: 2020-12-09 17:12:19 type: article metadata_visibility: show creators_name: Lesne, J creators_name: Locard-Paulet, M creators_name: Parra, J creators_name: Zivković, D creators_name: Menneteau, T creators_name: Bousquet, M-P creators_name: Burlet-Schiltz, O creators_name: Marcoux, J title: Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G03 keywords: Mass spectrometry, Proteasome, Structural biology, Supramolecular assembly note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. abstract: Hydrogen-Deuterium eXchange coupled to Mass Spectrometry (HDX-MS) is now common practice in structural biology. However, it is most of the time applied to rather small oligomeric complexes. Here, we report on the use of HDX-MS to investigate conformational differences between the human standard 20S (std20S) and immuno 20S (i20s) proteasomes alone or in complex with PA28αβ or PA28γ activators. Their solvent accessibility is analyzed through a dedicated bioinformatic pipeline including stringent statistical analysis and 3D visualization. These data confirm the existence of allosteric differences between the std20S and i20S at the surface of the α-ring triggered from inside the catalytic β-ring. Additionally, binding of the PA28 regulators to the 20S proteasomes modify solvent accessibility due to conformational changes of the β-rings. This work is not only a proof-of-concept that HDX-MS can be used to get structural insights on large multi-protein complexes in solution, it also demonstrates that the binding of the std20S or i20S subtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pair. date: 2020-12-01 date_type: published official_url: https://doi.org/10.1038/s41467-020-19934-z oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1833886 doi: 10.1038/s41467-020-19934-z pii: 10.1038/s41467-020-19934-z lyricists_name: Menneteau, Thomas lyricists_id: TMENN45 actors_name: Austen, Jennifer actors_id: JAUST66 actors_role: owner full_text_status: public publication: Nature Communications volume: 11 article_number: 6140 event_location: England citation: Lesne, J; Locard-Paulet, M; Parra, J; Zivković, D; Menneteau, T; Bousquet, M-P; Burlet-Schiltz, O; Lesne, J; Locard-Paulet, M; Parra, J; Zivković, D; Menneteau, T; Bousquet, M-P; Burlet-Schiltz, O; Marcoux, J; - view fewer <#> (2020) Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks. Nature Communications , 11 , Article 6140. 10.1038/s41467-020-19934-z <https://doi.org/10.1038/s41467-020-19934-z>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10116858/1/s41467-020-19934-z.pdf