Structural Basis of the Ca2+ Inhibitory Mechanism of Drosophila Na+/Ca2+ Exchanger CALX and Its Modification by Alternative Splicing
作者： Mousheng Wu , Shuilong Tong , Jennifer Gonzalez , Vasanthi Jayaraman , John L. Spudich
DOI: 10.1016/J.STR.2011.07.008
关键词: Biophysics 、 Plasma protein binding 、 Gene isoform 、 Biology 、 Biochemistry 、 Sodium-calcium exchanger 、 Protein structure 、 Calx 、 Drosophila Protein 、 Binding site 、 Alternative splicing
摘要: Summary The Na + /Ca 2+ exchanger CALX promotes Ca efflux in Drosophila sensory neuronal cells to facilitate light-mediated homeostasis. activity is negatively regulated by specific interaction within its two intracellular regulatory domains CBD1 and CBD2, yet how the binding converted molecular motion operate unknown. Here, we report crystal structures of entire domain CBD12 from alternative splicing isoforms, 1.1 1.2, exhibiting distinct dependency. show an open V-shaped conformation with four ions bound on CBD interface, confirmed LRET analysis. together -binding analysis support that inhibition achieved interdomain conformational changes induced at CBD1. difference between isoforms also indicates adjusts orientation angle modify property exchangers.
rcsb.org
core.ac.uk
elsevier.com参考文章(28)
MORDECAI P. BLAUSTEIN, GIOVANNI FONTANA, ROBERT S. ROGOWSKI, The Na+-Ca2+ Exchanger in Rat Brain Synaptosomes Annals of the New York Academy of Sciences. ,vol. 779, pp. 300- 317 ,(1996) , 10.1111/J.1749-6632.1996.TB44803.X
S Matsuoka, D A Nicoll, L V Hryshko, D O Levitsky, J N Weiss, K D Philipson, Regulation of the cardiac Na(+)-Ca2+ exchanger by Ca2+. Mutational analysis of the Ca(2+)-binding domain. The Journal of General Physiology. ,vol. 105, pp. 403- 420 ,(1995) , 10.1085/JGP.105.3.403
Mousheng Wu, Meitian Wang, Jay Nix, Larry V. Hryshko, Lei Zheng, Crystal Structure of CBD2 from the Drosophila Na+/Ca2+ Exchanger: Diversity of Ca2+ Regulation and Its Alternative Splicing Modification Journal of Molecular Biology. ,vol. 387, pp. 104- 112 ,(2009) , 10.1016/J.JMB.2009.01.045
Tao Wang, Hong Xu, Johannes Oberwinkler, Yuchun Gu, Roger C. Hardie, Craig Montell, Light Activation, Adaptation, and Cell Survival Functions of the Na+/Ca2+ Exchanger CalX Neuron. ,vol. 45, pp. 367- 378 ,(2005) , 10.1016/J.NEURON.2004.12.046
Donald M. Bers, Excitation-Contraction Coupling and Cardiac Contractile Force ,(1993)
DEBORA A. NICOLL, MICHELA OTTOLIA, KENNETH D. PHILIPSON, Toward a topological model of the NCX1 exchanger. Annals of the New York Academy of Sciences. ,vol. 976, pp. 11- 18 ,(2006) , 10.1111/J.1749-6632.2002.TB04709.X
Chris Dyck, Krista Maxwell, John Buchko, Michael Trac, Alexander Omelchenko, Mark Hnatowich, Larry V. Hryshko, Structure-Function Analysis of CALX1.1, a Na+-Ca2+ Exchanger fromDrosophila MUTAGENESIS OF IONIC REGULATORY SITES Journal of Biological Chemistry. ,vol. 273, pp. 12981- 12987 ,(1998) , 10.1074/JBC.273.21.12981
G. Ramanoudjame, M. Du, K. A. Mankiewicz, V. Jayaraman, Allosteric mechanism in AMPA receptors: a FRET-based investigation of conformational changes. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 103, pp. 10473- 10478 ,(2006) , 10.1073/PNAS.0603225103
Debora A. Nicoll, Michael R. Sawaya, Seunghyug Kwon, Duilio Cascio, Kenneth D. Philipson, Jeff Abramson, The Crystal Structure of the Primary Ca2+ Sensor of the Na+/Ca2+ Exchanger Reveals a Novel Ca2+ Binding Motif Journal of Biological Chemistry. ,vol. 281, pp. 21577- 21581 ,(2006) , 10.1074/JBC.C600117200
Mark Hilge, Jan Aelen, Geerten W. Vuister, Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+ sensors Molecular Cell. ,vol. 22, pp. 15- 25 ,(2006) , 10.1016/J.MOLCEL.2006.03.008