Crystal structure of the EF-hand parvalbumin at atomic resolution (0.91 angstrom) and at low temperature (100 K). Evidence for conformational multistates within the hydrophobic core

Several crystal structures of parvalbumin (Parv), a typical EF-hand protein , have been reported so far for different species with the best resolution achieving 1.5 Angstrom. Using a crystal grown under microgravity conditions , cryotechniques (100 K), and synchrotron radiation, it has now been possib le to determine the crystal structure of the fully Ca2+-loaded form of pike (component pI 4.10) Parv.Ca-2 at atomic resolution (0.91 Angstrom). The av ailability of such a high quality structure offers the opportunity to contr ibute to the definition of the validation tools useful for the refinement o f protein crystal structures determined to lower resolution. Besides a bett er definition of most of the elements in the protein three-dimensional stru cture than in previous studies, the high accuracy thus achieved allows the detection of well-defined alternate conformations, which are observed for 1 6 residues out of 107 in total. Among them, six occupy an internal position within the hydrophobic core and converge toward two small buried cavities with a total volume of about 60 Angstrom(3). There is no indication of any water molecule present in these cavities. It is probable that at temperatur es of physiological conditions there is a dynamic interconversion between t hese alternate conformations in an energy-barrier dependent manner. Such mo tions for which the amplitudes are provided by the present study will be as sociated with a time-dependent remodeling of the void internal space as par t of a slow dynamics regime (millisecond timescales) of the parvalbumin mol ecule. The relevance of such internal dynamics to function is discussed.