title: EF-hand protein dynamics and evolution of calcium signal transduction: an NMR view.
abstract: Calcium signaling, one of the most widespread signaling mechanisms in cells, is generally carried out by EF-hand proteins, characterized by a helix-loop-helix motif paired in functional domains. EF-hand proteins may be viewed as molecular switches activated by calcium concentration transients. The EF-hand structural database has grown to a point where meaningful inferences on the functional conformational rearrangements upon calcium binding can be made by comparing a fair number of pairs of end points, i.e., the structures of the apo and calcium-bound forms. More compact descriptors of the movement associated with calcium binding, in terms of principal component analysis of the six interhelical angles, have also become available. Dynamic information obtained by NMR, also with the aid of calcium substitution with paramagnetic lanthanides, is shedding light on the intrinsic amplitude of the conformational degrees of freedom sampled by the various members of the EF-hand superfamily, as well as on the time scales of the motions. Particularly, NMR of lanthanide derivatives helps in capturing long time scale motions. Both static and dynamic pictures reveal a large variety of behaviors. It is increasingly recognized that the EF-hand machinery has differentiated its behavior during evolution in several ways, e.g., by modifying one of the loops, by undergoing a further duplication after the initial motif duplication that originated the functional domain, or by acquiring the ability to dimerize.
authors.affiliation: Department of Food Science, University of Bologna, Piazza G. Goidanich 60, 47023, Cesena, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Capozzi
authors.forename: Federica
authors.initials: F
authors.lastname: Casadei
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchinat
mesh_terms: D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000737:chemistry; D020832:EF Hand Motifs; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation
chemical_list: D002135:Calcium-Binding Proteins