3U1N

Structure of the catalytic core of human SAMHD1

3U1N の概要

• エントリーDOI: 10.2210/pdb3u1n/pdb
• 分子名称: SAM domain and HD domain-containing protein 1, PHOSPHATE ION, ZINC ION, ... (4 entities in total)
• 機能のキーワード: hd-domain, deoxynucleotide triphosphohydrolase, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus : Q9Y3Z3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 246727.97

構造登録者

Goldstone, D.C.,Ennis-Adeniran, V.,Walker, P.A.,Haire, L.F.,Webb, M.,Taylor, I.A. (登録日: 2011-09-30, 公開日: 2011-11-16, 最終更新日: 2024-10-16)

主引用文献

Goldstone, D.C.,Ennis-Adeniran, V.,Hedden, J.J.,Groom, H.C.,Rice, G.I.,Christodoulou, E.,Walker, P.A.,Kelly, G.,Haire, L.F.,Yap, M.W.,de Carvalho, L.P.,Stoye, J.P.,Crow, Y.J.,Taylor, I.A.,Webb, M.
HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase
Nature, 480:379-382, 2011

PubMed Abstract: SAMHD1, an analogue of the murine interferon (IFN)-γ-induced gene Mg11 (ref. 1), has recently been identified as a human immunodeficiency virus-1 (HIV-1) restriction factor that blocks early-stage virus replication in dendritic and other myeloid cells and is the target of the lentiviral protein Vpx, which can relieve HIV-1 restriction. SAMHD1 is also associated with Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy characterized by chronic cerebrospinal fluid lymphocytosis and elevated levels of the antiviral cytokine IFN-α. The pathology associated with AGS resembles congenital viral infection, such as transplacentally acquired HIV. Here we show that human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate. The crystal structure of the catalytic core of SAMHD1 reveals that the protein is dimeric and indicates a molecular basis for dGTP stimulation of catalytic activity against dNTPs. We propose that SAMHD1, which is highly expressed in dendritic cells, restricts HIV-1 replication by hydrolysing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis.

PubMed: 22056990
DOI: 10.1038/nature10623

実験手法

X-RAY DIFFRACTION (3.1 Å)