Fig. 1.

Q141K gout-causing mutation changes NBD structure in a model of ABCG2. A: model comparing Wt and Q141K NBDs as described in Woodward et al. (32) reveals a shift in an adjacent loop (black arrow, Q141K in blue, Wt in green). B: the H155 residue at the top of the loop clashes with the mutant 141K, causing a loop shift and is corrected in the model with a 155A substitution. C: biochemical confirmation of the model shows the Q141K mutant expression levels can be rescued with the secondary H155A substitution. HEK293 cells were transiently transfected with ABCG2 constructs. Total protein was measured and normalized to GAPDH loading control and Wt ABCG2 expression from same Western blot. For details, see Ref. 32. D: summary data. Values are means ± SE, Student's t-test; n = 4. **P < 0.0001.