Molecular mechanism of the calcium-induced conformational change in the spectrin EF-hands.
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.
Travé
G
G
European Molecular Biology Laboratory, Heidelberg, Germany.
Lacombe
P J
PJ
Pfuhl
M
M
Saraste
M
M
Pastore
A
A
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
D014336:Troponin; D019209:Troponin C; D013049:Spectrin; D002118:Calcium