citation_mjid: pnas;117/6/2948 og-title: Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2 article:published_time: 2020-02-11 twitter:card: summary_large_image citation_reference: citation_journal_title=Nature reviews. Molecular cell biology;citation_journal_abbrev=Nat Rev Mol Cell Biol;citation_author=H. J. Dyson;citation_author=P. E. Wright;citation_title=Intrinsically unstructured proteins and their functions.;citation_pages=197-208;citation_volume=6;citation_year=2005;citation_issue=3;citation_pmid=15738986;citation_doi=10.1038/nrm1589 citation_journal_title: Proceedings of the National Academy of Sciences type: article citation_author_email: Markus.Zweckstetter@dzne.de citation_issn: 0027-8424 citation_full_html_url: https://www.pnas.org/content/117/6/2948.full citation_public_url: https://www.pnas.org/content/117/6/2948 dc:title: Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2 | PNAS Content-Encoding: UTF-8 citation_pdf_url: https://www.pnas.org/content/pnas/117/6/2948.full.pdf citation_section: PNAS Plus citation_num_pages: 9 citation_lastpage: 2956 citation_fulltext_world_readable: citation_journal_abbrev: PNAS DC.Identifier: 10.1073/pnas.1907960117 DC.Rights: Copyright © 2020 the Author(s). Published by PNAS.. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). citation_author: Florian Hamann citation_abstract_html_url: https://www.pnas.org/content/117/6/2948.abstract citation_issue: 6 og-image: https://www.pnas.org/sites/default/files/highwire/pnas/117/6.cover-source.jpg HW.identifier: /pnas/117/6/2948.atom citation_doi: 10.1073/pnas.1907960117 citation_volume: 117 Content-Language: en format-detection: telephone=no Generator: Drupal 7 (http://drupal.org) citation_author_orcid: http://orcid.org/0000-0002-2536-6581 DC.AccessRights: open-access citation_publication_date: 2020/02/11 citation_title: Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2 citation_author_institution: Georg-August-University Göttingen citation_publisher: National Academy of Sciences citation_id: 117/6/2948 og-type: article title: Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2 | PNAS twitter:image: https://www.pnas.org/sites/default/files/highwire/pnas/117/6.cover-source.jpg og-url: https://www.pnas.org/content/117/6/2948 DC.Description: The G-patch domain is found in eukaryotic and viral proteins involved in protein?protein and protein?nucleic acid interactions. Some G-patch proteins play a vital role in the spliceosome by stimulating the DEAH-box ATPases Prp2 and Prp43; however, their structural characterization and exact binding mode have remained elusive. By studying the Prp2-specific G-patch domain of Spp2 by means of X-ray crystallography and nuclear magnetic resonance spectroscopy, we could show that the G-patch is mostly disordered in solution but adopts a defined fold on binding to Prp2. The disordered nature of Spp2 might be important for the positioning of Prp2 during its recruitment to the spliceosome. og-description: The G-patch domain is found in eukaryotic and viral proteins involved in protein?protein and protein?nucleic acid interactions. Some G-patch proteins play a vital role in the spliceosome by stimulating the DEAH-box ATPases Prp2 and Prp43; however, their structural characterization and exact binding mode have remained elusive. By studying the Prp2-specific G-patch domain of Spp2 by means of X-ray crystallography and nuclear magnetic resonance spectroscopy, we could show that the G-patch is mostly disordered in solution but adopts a defined fold on binding to Prp2. The disordered nature of Spp2 might be important for the positioning of Prp2 during its recruitment to the spliceosome. Content-Type-Hint: text/html; charset=utf-8 DC.Format: text/html DC.Publisher: National Academy of Sciences DC.Contributor: Florian Hamann Content-Type: application/xhtml+xml; charset=UTF-8 X-Parsed-By: org.apache.tika.parser.DefaultParser article:section: PNAS Plus citation_pmid: 31974312 twitter:title: Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2 citation_article_type: Research Article citation_abstract:

The spliceosome consists of five small RNAs and more than 100 proteins. Almost 50% of the human spliceosomal proteins were predicted to be intrinsically disordered or to contain disordered regions, among them the G-patch protein Spp2. The G-patch region of Spp2 binds to the DEAH-box ATPase Prp2, and both proteins together are essential for promoting the transition from the Bact to the catalytically active B* spliceosome. Here we show by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy that Spp2 is intrinsically disordered in solution. Crystal structures of a complex consisting of Prp2-ADP and the G-patch domain of Spp2 demonstrate that the G-patch gains a defined fold when bound to Prp2. While the N-terminal region of the G-patch always folds into an ?-helix in five different crystal structures, the C-terminal part is able to adopt two alternative conformations. NMR studies further revealed that the N-terminal part of the Spp2 G-patch, which is the most conserved region in different G-patch proteins, transiently samples helical conformations, possibly facilitating a conformational selection binding mechanism. The structural analysis unveils the role of conserved residues of the G-patch in the dynamic interaction mode of Spp2 with Prp2, which is vital to maintain the binding during the Prp2 domain movements needed for RNA translocation.

DC.Title: Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2 issue_cover_image: https://www.pnas.org/sites/default/files/highwire/pnas/117/6.cover-source.jpg citation_firstpage: 2948 viewport: initial-scale=1, maximum-scale=1, width=device-width, user-scalable=yes HW.pisa: pnas;117/6/2948 DC.Language: en twitter:description: The G-patch domain is found in eukaryotic and viral proteins involved in protein?protein and protein?nucleic acid interactions. Some G-patch proteins play a vital role in the spliceosome by stimulating the DEAH-box ATPases Prp2 and Prp43; however, their structural characterization and exact binding mode have remained elusive. By studying the Prp2-specific G-patch domain of Spp2 by means of X-ray crystallography and nuclear magnetic resonance spectroscopy, we could show that the G-patch is mostly disordered in solution but adopts a defined fold on binding to Prp2. The disordered nature of Spp2 might be important for the positioning of Prp2 during its recruitment to the spliceosome. DC.Date: 2020-02-11 citation_access: all og-site-name: PNAS category: research-article