Preliminary structure analysis of the DH/PH domains of leukemia-associated RhoGEF

Leukemia‐associated RhoGEF (LARG) is a multidomain protein that relays signals from Gα12/13‐coupled heptahelical receptors to GTPases that regulate the cytoskeleton. To understand the molecular basis of LARG‐mediated signal transduction, structural analysis of its DH/PH domains has been initiated. The LARG DH/PH domains have been overexpressed in Escherichia coli as a TEV protease‐cleavable fusion protein containing maltose‐binding protein and a hexahistidine tag at the N‐ and C‐termini, respectively. Crystals of the DH/PH domains were obtained (space group C2; unit‐cell parameters a = 195.5, b = 46.0, c = 75.1 Å, β = 105.0°) and xenon and NaBr derivatives were generated which should allow the structure to be determined by MIRAS.