8uzt
From Proteopedia
Mitochondrial single-stranded binding protein bound to DNA
Structural highlights
FunctionSSBP_HUMAN This protein binds preferentially and cooperatively to ss-DNA. Probably involved in mitochondrial DNA replication. Associates with mitochondrial DNA. Publication Abstract from PubMedThe mitochondrial single-stranded DNA (ssDNA) binding protein, mtSSB or SSBP1, binds to ssDNA to prevent secondary structures of DNA that could impede downstream replication or repair processes. Clinical mutations in the SSBP1 gene have been linked to a range of mitochondrial disorders affecting nearly all organs and systems. Yet, the molecular determinants governing the interaction between mtSSB and ssDNA have remained elusive. Similarly, the structural interaction between mtSSB and other replisome components, such as the mitochondrial DNA polymerase, Polgamma, has been minimally explored. Here, we determined a 1.9-A X-ray crystallography structure of the human mtSSB bound to ssDNA. This structure uncovered two distinct DNA binding sites, a low-affinity site and a high-affinity site, confirmed through site-directed mutagenesis. The high-affinity binding site encompasses a clinically relevant residue, R38, and a highly conserved DNA base stacking residue, W84. Employing cryo-electron microscopy, we confirmed the tetrameric assembly in solution and capture its interaction with Polgamma. Finally, we derived a model depicting modes of ssDNA wrapping around mtSSB and a region within Polgamma that mtSSB binds. Structures of the mitochondrial single-stranded DNA binding protein with DNA and DNA polymerase gamma.,Riccio AA, Bouvette J, Pedersen LC, Somai S, Dutcher RC, Borgnia MJ, Copeland WC Nucleic Acids Res. 2024 Aug 6:gkae670. doi: 10.1093/nar/gkae670. PMID:39106165[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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