HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase

David C. Goldstone, Valerie Ennis-Adeniran, Joseph J. Hedden, Harriet C. T. Groom, Gillian I. Rice, Evangelos Christodoulou, Philip A. Walker, Geoff Kelly, Lesley F. Haire, Melvyn W. Yap, Luiz Pedro S. de Carvalho, Jonathan P. Stoye, Yanick J. Crow, Ian A. Taylor () and Michelle Webb ()
Additional contact information
David C. Goldstone: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Valerie Ennis-Adeniran: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Joseph J. Hedden: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Harriet C. T. Groom: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Gillian I. Rice: Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre, Central Manchester Foundation Trust University Hospitals
Evangelos Christodoulou: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Philip A. Walker: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Geoff Kelly: MRC Biomedical NMR Centre, National Institute for Medical Research, the Ridgeway, Mill Hill
Lesley F. Haire: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Melvyn W. Yap: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Luiz Pedro S. de Carvalho: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Jonathan P. Stoye: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Yanick J. Crow: Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre, Central Manchester Foundation Trust University Hospitals
Ian A. Taylor: MRC National Institute for Medical Research, the Ridgeway, Mill Hill
Michelle Webb: Genetic Medicine, University of Manchester, Manchester Academic Heath Science Centre, Central Manchester Foundation Trust University Hospitals

Nature, 2011, vol. 480, issue 7377, 379-382

Abstract: Antiretroviral role for SAMHD1 protein Mutations in SAMHD1 protein are associated with the human autoimmune disease Aicardi–Goutières syndrome, and SAMHD1 was recently shown to be responsible for restriction of HIV-1 replication in myeloid cells. Ian Taylor and colleagues reveal a previously unknown function of SAMHD1 that could explain its antivirus role. They provide a crystal structure of the catalytic core of SAMHD1 and show that it is a dGTP-stimulated triphosphohydrolase that hydrolyses dNTPs, the building blocks of DNA. This activity may prevent reverse transcription and viral synthesis of complementary DNA by keeping the concentration of cellular dNTPs at a low level.

Date: 2011
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DOI: 10.1038/nature10623

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