BioMed Research International / 2015 / Article / Fig 3

Research Article

SAMHD1 Gene Mutations Are Associated with Cerebral Large-Artery Atherosclerosis

Figure 3

SAMHD1 mutations from individuals with stroke diminish SAMHD1 tetramerisation and dNTP hydrolase activity. (a) The crystal structure of the tetrameric SAMHD1 catalytic core (residues 113–626; PDB ID, 4BZB) is shown with the position of residue E281 () indicated. Residues 278–283 (SPVEDS) were not resolved [17]. Each subunit is rendered with a different colour. (b) SAMHD1 stroke patient mutations interfere with SAMHD1 tetramerisation. Wild type and mutant recombinant SAMHD1 proteins (250 nM) were preincubated with dGTP (25 μM), and the mixtures were separated on an analytical gel filtration column. The peaks corresponding to SAMHD1 tetramers, dimers/monomers, and dGTP are indicated. (c) The extent of SAMHD1 tetramerisation was determined with various concentrations of dGTP (0 to 200 μM) as described in (b). (d) dGTP-dependent dGTPase activity of recombinant SAMHD1. The standard error from triplicate samples is shown.