title: Molecular mechanism of the calcium-induced conformational change in the spectrin EF-hands.
abstract: Calcium is a universally employed cytosolic messenger in eukaryotic cells. Most of the proteins that bind signalling calcium are members of the calmodulin superfamily and share two or more helix-loop-helix motifs known as EF-hands. A model, based on structure comparison of different domains and supported by preliminary NMR data, has suggested that EF-hands involved in signal transduction undergo a major conformational change upon calcium binding from a 'closed' to an 'open' state allowing protein-protein interaction. We have determined the solution structures of the EF-hand pair from alpha-spectrin in the absence and in the presence of calcium. The structures are in the closed and open conformation respectively, providing a definite experimental proof for the closed-to-open model. Our results allow formulation of the rules which govern the movement induced by calcium. These rules may be generalized to other EF-hands since the key residues involved are conserved within the calmodulin family.
authors.affiliation: European Molecular Biology Laboratory, Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Travé
authors.forename: P J
authors.initials: PJ
authors.lastname: Lacombe
authors.forename: M
authors.initials: M
authors.lastname: Pfuhl
authors.forename: M
authors.initials: M
authors.lastname: Saraste
authors.forename: A
authors.initials: A
authors.lastname: Pastore
mesh_terms: D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D013049:Spectrin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D014336:Troponin / Q000737:chemistry; D019209:Troponin C
chemical_list: D014336:Troponin; D019209:Troponin C; D013049:Spectrin; D002118:Calcium