Journal
PROTEIN SCIENCE
Volume 30, Issue 9, Pages 1757-1775Publisher
WILEY
DOI: 10.1002/pro.4140
Keywords
genome guardian; OB-fold; PXXP; SH3 domain; SSB
Categories
Funding
- National Institute of General Medical Sciences [GM10056]
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The single-stranded DNA binding protein (SSB) plays a crucial role in DNA metabolism in bacteria, interacting with at least 20 partner proteins to regulate their activities through the linker/OB-fold network. This network of interactions results in cooperative ssDNA-binding and dynamic behavior of tetramers along the ssDNA lattice, essential for downstream DNA processing events. The SSB interactome is classified as the first family of prokaryotic, oligosaccharide/oligonucleotide binding fold (OB-fold) genome guardians due to the critical role of OB-folds in the linker/OB-fold network of interactions.
The single-stranded DNA binding protein (SSB) is essential to all aspects of DNA metabolism in bacteria. This protein performs two distinct, but closely intertwined and indispensable functions in the cell. SSB binds to single-stranded DNA (ssDNA) and at least 20 partner proteins resulting in their regulation. These partners comprise a family of genome guardians known as the SSB interactome. Essential to interactome regulation is the linker/OB-fold network of interactions. This network of interactions forms when one or more PXXP motifs in the linker of SSB bind to an OB-fold in a partner, with interactome members involved in competitive binding between the linker and ssDNA to their OB-fold. Consequently, when linker-binding occurs to an OB-fold in an interactome partner, proteins are loaded onto the DNA. When linker/OB-fold interactions occur between SSB tetramers, cooperative ssDNA-binding results, producing a multi-tetrameric complex that rapidly protects the ssDNA. Within this SSB-ssDNA complex, there is an extensive and dynamic network of linker/OB-fold interactions that involves multiple tetramers bound contiguously along the ssDNA lattice. The dynamic behavior of these tetramers which includes binding mode changes, sliding as well as DNA wrapping/unwrapping events, are likely coupled to the formation and disruption of linker/OB-fold interactions. This behavior is essential to facilitating downstream DNA processing events. As OB-folds are critical to the essence of the linker/OB-fold network of interactions, and they are found in multiple interactome partners, the SSB interactome is classified as the first family of prokaryotic, oligosaccharide/oligonucleotide binding fold (OB-fold) genome guardians.
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