The first group of residues I557, G559, V572, and G576 is located at the dimerization interface of the C-lobe and mutation of these residues may interfere with dimerization of the kinase domain. It is noteworthy that kinase domain dimerization does not affect the solvent accessibility of G576 (Table 1 ), indicating that G576 is not directly involved in dimerization. The amino acid side chain of a mutant at this position would point into a hydrophobic niche that also accommodates the side chain of L574 from another monomer. The G576E mutation would exert both charge and space hindrances on the side chain of L574 and thus disrupt the dimerization (Figure 7) , consistent with the previous observation that the G576E mutant of the full length GNE remains as a trimer [11] .