The model did not come to Eck immediately. “We stared at the structure for about a year,” he says. But then the group tried to reconcile the perfect twofold symmetry of the FH2 crystal structure with the helical alignment of actin monomers in a filament. The only way the two would come together, they realized, was if the FH2 was flexible.
A prime suspect for the source of flexibility was a linker region of FH2. It was relatively unstructured in the crystal, could be clipped by proteases, and was the only significant tie between two parts of the dimer. Sure enough, a crystal of a mutant FH2 that was still functional had a completely different orientation of the linker and thus of the two parts of FH2.
Eck believes the two structures prove flexibility rather than demonstrating the two most important orientations of the FH2 regions. Eck hopes that eventually he will see oscillations in fluorescence resonance energy transfer (FRET) as the FH2 steps alternately close to and far away from the monomers of a growing actin filament. ▪