Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein
- The family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately 100 kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA and RNA binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerize, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species.
Author: | Sophie M. KornORCiDGND, Julian von EhrORCiD, Karthikeyan DhamotharanORCiDGND, Jan-Niklas TantsORCiD, Rupert AbeleORCiDGND, Andreas SchlundtORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-751160 |
DOI: | https://doi.org/10.3390/ijms24043286 |
ISSN: | 1422-0067 |
Parent Title (English): | International Journal of Molecular Sciences |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/02/07 |
Date of first Publication: | 2023/02/07 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/09/07 |
Tag: | RNA processing; RRM domain; SAP domain; chromatin; dual nucleic acid binding; nuclear magnetic resonance spectroscopy; nuclear matrix; protein dynamics; scaffold attachment factor proteins |
Volume: | 24 |
Issue: | 4, art. 3286 |
Article Number: | 3286 |
Page Number: | 22 |
HeBIS-PPN: | 513653015 |
Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ) | |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |