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5AO3

Crystal structure of human SAMHD1 (amino acid residues 115-626) bound to GTP

Summary for 5AO3
Entry DOI10.2210/pdb5ao3/pdb
Related5AO0 5AO1 5AO2 5AO4
DescriptorDEOXYNUCLEOSIDE TRIPHOSPHATE TRIPHOSPHOHYDROLASE SAMHD1, FE (III) ION, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
Functional Keywordshydrolase, deoxynucleoside triphosphate triphosphohydrolase, hiv restriction factor
Biological sourceHOMO SAPIENS (HUMAN)
Cellular locationNucleus : Q9Y3Z3
Total number of polymer chains4
Total formula weight252469.36
Authors
Schwefel, D.,Taylor, I.A. (deposition date: 2015-09-09, release date: 2016-04-20, Last modification date: 2024-10-23)
Primary citationArnold, L.H.,Groom, H.C.T.,Kunzelmann, S.,Schwefel, D.,Caswell, S.J.,Ordonez, P.,Mann, M.C.,Rueschenbaum, S.,Goldstone, D.C.,Pennell, S.,Howell, S.A.,Stoye, J.P.,Webb, M.,Taylor, I.A.,Bishop, K.N.
Phospho-Dependent Regulation of Samhd1 Oligomerisation Couples Catalysis and Restriction.
Plos Pathog., 11:5194-, 2015
Cited by
PubMed Abstract: SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells. Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase activity that reduces cellular dNTP to a level where reverse transcriptase cannot function, although alternative mechanisms have been proposed recently. Here, we present combined structural and virological data demonstrating that in addition to allosteric activation and triphosphohydrolase activity, restriction correlates with the capacity of SAMHD1 to form "long-lived" enzymatically competent tetramers. Tetramer disruption invariably abolishes restriction but has varied effects on in vitro triphosphohydrolase activity. SAMHD1 phosphorylation also ablates restriction and tetramer formation but without affecting triphosphohydrolase steady-state kinetics. However phospho-SAMHD1 is unable to catalyse dNTP turnover under conditions of nucleotide depletion. Based on our findings we propose a model for phosphorylation-dependent regulation of SAMHD1 activity where dephosphorylation switches housekeeping SAMHD1 found in cycling cells to a high-activity stable tetrameric form that depletes and maintains low levels of dNTPs in differentiated cells.
PubMed: 26431200
DOI: 10.1371/JOURNAL.PPAT.1005194
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.004 Å)
Structure validation

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