Backbone 1 H, 13 C and 15 N resonance assignments of the OB domain of the single stranded DNA-binding protein hSSB2 (NABP1/OBFC2A) and chemical shift mapping of the DNA-binding interface

Single stranded DNA-binding proteins (SSBs) are essential for the maintenance of genome integrity and are required in in all known cellular organisms. Over the last 10 years, the role of two new human SSBs, hSSB1 (NABP2/OBFC2B) and hSSB2 (NABP1/OBFC2A), has been described and characterised in variou...

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Bibliographic Details
Published inBiomolecular NMR assignments Vol. 12; no. 1; p. 107
Main Authors Kariawasam, Ruvini, Knight, Maddison, Gamsjaeger, Roland, Cubeddu, Liza
Format Journal Article
LanguageEnglish
Published Netherlands 01.04.2018
Subjects
Binding Sites
DNA, Single-Stranded - metabolism
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - metabolism
Humans
Nuclear Magnetic Resonance, Biomolecular
Protein Binding
Protein Domains
NMR
SSBs
hSSB1
hSSB2
DNA repair
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Summary:Single stranded DNA-binding proteins (SSBs) are essential for the maintenance of genome integrity and are required in in all known cellular organisms. Over the last 10 years, the role of two new human SSBs, hSSB1 (NABP2/OBFC2B) and hSSB2 (NABP1/OBFC2A), has been described and characterised in various important DNA repair processes. Both these proteins are made up of a conserved oligonucleotide-binding (OB) fold that is responsible for ssDNA recognition as well a unique flexible carboxy-terminal extension involved in protein-protein interactions. Due to their similar domain organisation, hSSB1 and hSSB2 have been found to display some overlapping functions. However, several studies have also revealed cell- and tissue-specific roles for these two proteins, most likely due to small but significant differences in the protein sequence of the OB domains. While the molecular details of ssDNA binding by hSSB1 has been studied extensively, comparatively little is known about hSSB2. In this study, we use NMR solution-state backbone resonance assignments of the OB domain of hSSB2 to map the ssDNA interaction interface. Our data reveal that ssDNA binding by hSSB2 is driven by four key aromatic residues in analogy to hSSB1, however, some significant differences in the chemical shift perturbations are observed, reflecting differences in ssDNA recognition. Future studies will aim at determining the structural basis of these differences and thus help to gain a more comprehensive understanding of the functional divergences that these novel hSSBs display in the context of genome maintenance.
ISSN:1874-270X