6U6Z

Human SAMHD1 bound to deoxyribo(TG*TTCA)-oligonucleotide

6U6Z の概要

• エントリーDOI: 10.2210/pdb6u6z/pdb
• 分子名称: Deoxynucleoside triphosphate triphosphohydrolase SAMHD1, DNA polymer TG(PST)TCA, ZINC ION, ... (4 entities in total)
• 機能のキーワード: samhd1, hiv, restriction factor, innate immunity, dntpase, deoxyribo-oligonucleotide, phosphorothioate, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 254644.51

構造登録者

Taylor, A.B.,Yu, C.H.,Ivanov, D.N. (登録日: 2019-08-30, 公開日: 2020-09-02, 最終更新日: 2023-10-11)

主引用文献

Yu, 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

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

実験手法

X-RAY DIFFRACTION (2.1 Å)