8TDW

ssRNA bound SAMHD1 T open

Summary for 8TDW

• Entry DOI: 10.2210/pdb8tdw/pdb
• EMDB information: 41175
• Descriptor: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, RNA (5'-R(P*CP*CP*GP*GP*CP*C)-3'), RNA (5'-R(P*CP*CP*GP*AP*CP*C)-3'), ... (4 entities in total)
• Functional Keywords: deoxynucleoside triphosphate triphosphohydrolase, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 293049.71

Authors

Sung, M.,Huynh, K.,Han, S. (deposition date: 2023-07-05, release date: 2023-11-22, Last modification date: 2023-12-20)

Primary citation

Orris, B.,Sung, M.W.,Bhat, S.,Xu, Y.,Huynh, K.W.,Han, S.,Johnson, D.C.,Bosbach, B.,Shields, D.J.,Stivers, J.T.
Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.
Nucleic Acids Res., 51:12443-12458, 2023

PubMed Abstract: 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.

PubMed: 37930833
DOI: 10.1093/nar/gkad971

Experimental method

ELECTRON MICROSCOPY (3.04 Å)