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Zenon Grabarek, Ph.D.
Principal Scientist
Muscle-related diseases, protein structure, calcium ions
Email: grabarek at bbri.org
 Research Summary
We aim to explain in structural terms how calcium ions regulate the contraction of muscles and other intracellular processes. The key step is the binding of Ca2+ to a specific calcium binding protein followed by a structural change that is then relayed to the respective target proteins. In smooth muscle the regulatory function is performed by calmodulin and the myosin light chain kinase, whereas the troponin-tropomyosin complex regulates the contraction in skeletal and cardiac muscles. We apply fluorescence spectroscopy, X-ray crystallography and other physicochemical techniques to the native and specifically mutated proteins of the regulatory complexes to learn how Ca2+ alters their structure and how these changes trigger the physiological response.
Figure. Comparison of various EF-hand motifs in a conformation-independent frame of reference defined by the central structure named EF-hand-beta-scaffold. For more detail see: Grabarek, Z., JMB 359:509,2006. |
Selected Publications
Grabarek Z. (2006) Structural basis for diversity of the EF-hand calcium-binding proteins. J Mol Biol. 359(3):509-525.
Chereau D, Kerff F, Graceffa P, Grabarek Z, Langsetmo K, Dominguez R. (2005) Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly. Proc Natl Acad Sci U S A. 102(46):16644-9.
Terrak M, Rebowski G, Lu RC, Grabarek Z, Dominguez R. (2005) Structure of the light chain-binding domain of myosin V. Proc Natl Acad Sci U S A. 102(36):12718-12723.
Gallant C, You JY, Sasaki Y, Grabarek Z, Morgan KG. (2005) MARCKS is a major PKC-dependent regulator of calmodulin targeting in smooth muscle. J Cell Sci. 118(Pt 16):3595-3605.
Grabarek Z. (2005) Structure of a trapped intermediate of calmodulin: calcium regulation of EF-hand proteins from a new perspective. J Mol Biol. 346(5):1351-1366.
Shen Y, Lee YS, Soelaiman S, Bergson P, Lu D, Chen A, Beckingham K, Grabarek Z, Mrksich M, Tang WJ. (2002) Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins. EMBO J. 21(24):6721-6732.
Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ. (2002) Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin. Nature. 415(6870):396-402.
PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)
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