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-Structure paper
タイトル | Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 51, Issue 22, Page 12443-12458, Year 2023 |
掲載日 | 2023年12月11日 |
著者 | Benjamin Orris / Min Woo Sung / Shridhar Bhat / Yingrong Xu / Kevin W Huynh / Seungil Han / Darren C Johnson / Benedikt Bosbach / David J Shields / James T Stivers / |
PubMed 要旨 | The dNTPase activity of tetrameric SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) plays a critical role in cellular dNTP regulation. SAMHD1 also associates ...The dNTPase activity of tetrameric SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) plays a critical role in cellular dNTP regulation. SAMHD1 also associates with stalled DNA replication forks, DNA repair foci, ssRNA and telomeres. The above functions require nucleic acid binding by SAMHD1, which may be modulated by its oligomeric state. Here we establish in cryo-EM and biochemical studies that the guanine-specific A1 activator site of each SAMHD1 monomer is used to target the enzyme to guanine nucleotides within single-stranded (ss) DNA and RNA. Remarkably, nucleic acid strands containing a single guanine base induce dimeric SAMHD1, while two or more guanines with ∼20 nucleotide spacing induce a tetrameric form. A cryo-EM structure of ssRNA-bound tetrameric SAMHD1 shows how ssRNA strands bridge two SAMHD1 dimers and stabilize the structure. This ssRNA-bound tetramer is inactive with respect to dNTPase and RNase activity. |
リンク | Nucleic Acids Res / PubMed:37930833 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.04 - 3.44 Å |
構造データ | EMDB-41174, PDB-8tdv: EMDB-41175, PDB-8tdw: |
化合物 | ChemComp-FE: |
由来 |
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キーワード | HYDROLASE / Deoxynucleoside triphosphate triphosphohydrolase |