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6U6X

Human SAMHD1 bound to deoxyribo(C*G*C*C*T)-oligonucleotide

Summary for 6U6X
Entry DOI10.2210/pdb6u6x/pdb
DescriptorDeoxynucleoside triphosphate triphosphohydrolase SAMHD1, DNA SC-GS-SC-SC-DT, ZINC ION, ... (4 entities in total)
Functional Keywordssamhd1, hiv, restriction factor, innate immunity, dntpase, deoxyribo-oligonucleotide, phosphorothioate, hydrolase
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains8
Total formula weight253304.73
Authors
Taylor, A.B.,Bhattacharya, A.,Wang, Z.,Ivanov, D.N. (deposition date: 2019-08-30, release date: 2020-09-02, Last modification date: 2024-10-09)
Primary citationYu, C.H.,Bhattacharya, A.,Persaud, M.,Taylor, A.B.,Wang, Z.,Bulnes-Ramos, A.,Xu, J.,Selyutina, A.,Martinez-Lopez, A.,Cano, K.,Demeler, B.,Kim, B.,Hardies, S.C.,Diaz-Griffero, F.,Ivanov, D.N.
Nucleic acid binding by SAMHD1 contributes to the antiretroviral activity and is enhanced by the GpsN modification.
Nat Commun, 12:731-731, 2021
Cited by
PubMed Abstract: SAMHD1 impedes infection of myeloid cells and resting T lymphocytes by retroviruses, and the enzymatic activity of the protein-dephosphorylation of deoxynucleotide triphosphates (dNTPs)-implicates enzymatic dNTP depletion in innate antiviral immunity. Here we show that the allosteric binding sites of the enzyme are plastic and can accommodate oligonucleotides in place of the allosteric activators, GTP and dNTP. SAMHD1 displays a preference for oligonucleotides containing phosphorothioate bonds in the Rp configuration located 3' to G nucleotides (GpsN), the modification pattern that occurs in a mechanism of antiviral defense in prokaryotes. In the presence of GTP and dNTPs, binding of GpsN-containing oligonucleotides promotes formation of a distinct tetramer with mixed occupancy of the allosteric sites. Mutations that impair formation of the mixed-occupancy complex abolish the antiretroviral activity of SAMHD1, but not its ability to deplete dNTPs. The findings link nucleic acid binding to the antiretroviral activity of SAMHD1, shed light on the immunomodulatory effects of synthetic phosphorothioated oligonucleotides and raise questions about the role of nucleic acid phosphorothioation in human innate immunity.
PubMed: 33531504
DOI: 10.1038/s41467-021-21023-8
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.58 Å)
Structure validation

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