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 dimerise, 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.

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Author:Sophie M. KornORCiDGND, Julian von EhrORCiD, Karthikeyan DhamotharanORCiDGND, Jan-Niklas TantsORCiD, Rupert AbeleORCiDGND, Andreas SchlundtORCiDGND
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2022/12/29
Date of first Publication:2022/12/29
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2023/08/09
Page Number:23
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Wissenschaftliche Zentren und koordinierte Programme / Zentrum f├╝r Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY-NC - Namensnennung - Nicht kommerziell 4.0 International