tailieunhanh - Báo cáo khoa học: Novel aspects of calmodulin target recognition and activation

Several crystal andNMRstructures of calmodulin (CaM)in complex with fragments derived from CaM-regulated pro-teins have been reported recently and reveal novel ways for CaMto interact with its targets. This review will discuss and compare features of the interaction between CaM and its target domains derived from the plasma membrane Ca 2+ -pump, the Ca 2+ -activated K + -channel, the Ca 2+ / CaM-dependent kinase kinase and the anthrax exotoxin. | Eur. J. Biochem. 270 404-414 2003 FEBS 2003 doi REVIEW ARTICLE Novel aspects of calmodulin target recognition and activation Stefan W. Vetter1 and Estelle Leclerc2 1 Department of Molecular Biology and 2Department of Immunology The Scripps Research Institute La Jolla CA USA Several crystal and NMR structures of calmodulin CaM in complex with fragments derived from CaM-regulated proteins have been reported recently and reveal novel ways for CaM to interact with its targets. This review will discuss and compare features of the interaction between CaM and its target domains derived from the plasma membrane Ca2 -pump the Ca2 -activated K -channel the Ca2 CaM-dependent kinase kinase and the anthrax exotoxin. Unexpected aspects of CaM target interaction observed in these complexes include a bínding of the Ca2 -pump domain to only the C-terminal part of CaM b dimer formation with fragments of the K -channel c ineerikn of CaM between two domains of the anthrax exotoxin d binding of Ca2 ions to only one EF-hand pair and e binding of CaM in an extended conformation to some of its targets. The mode of interaction between CaM and these targets differs from binding conformations previously observed between CaM and peptides derived from myosin light chain kinase MLCK and Ịií ndl m IthKiee IIa CaMKIIa . In the latter complexes CaM engulfs the CaMbinding domain peptide with its two Ca2 -binding lobes and forms a compact ellipsoid-like complex. In the early 1990s a model for the activation of CaM-regulated proteins was developed based on this observation and postulated activation through the displacement of an autoinhibitory or regulatory domain from the target protein upon binding of CaM. The novel structures of CaM-target complexes discussed here demonstrate that this mechanism of activation may be less general than previously believed and seems to be not valid for the anthrax exotoxin the CaM-regulated K -channel and possibly also not for