F. Capozzi, C. Luchinat, C. Micheletti and F. Pontiggia
Essential dynamics of helices provide a functional classification of EF-hand proteins
J. Proteome Res. 6 4245-4255 (2007)
Link to online article.
Low energy modes have been calculated for the largest possible number
of available representatives (>150) of EF-hand domains belonging to
different members of the calcium-binding EF-hand protein
superfamily. These proteins are the major actors in signal
transduction. The latter, in turn, relies on the dynamical properties
of the systems, in particular on the relative movements of the four
helices characterizing each EF-hand domain upon calcium binding. The
peculiar structural and dynamical features of this protein superfamily
are systematically investigated by a novel approach, where the lowest
energy (essential) modes are described in the space of the six
interhelical angles among the four helices constituting the EF-hand
domain. The modes, obtained through a general and transferable
coarse-graining scheme, identify the easy directions of helical
motions. It is found that, for most proteins, the two lowest energy
modes are sufficient to capture most of the helices' fluctuation
dynamics. Strikingly, the comparison of such modes for all possible
pairs of EF-hand domain representatives reveals that only few easy
directions are preferred within this large protein superfamily. This
enables us to introduce a novel dynamics-based classification of
EF-hand domains that complements existing structure-based
characterizations from an unexplored biological perspective.