2K0E

A Coupled Equilibrium Shift Mechanism in Calmodulin-Mediated Signal Transduction

Summary for 2K0E

• Entry DOI: 10.2210/pdb2k0e/pdb
• Related: 1J7O 1J7P 2K0F
• Descriptor: Calmodulin, CALCIUM ION (2 entities in total)
• Functional Keywords: ef hands, ensemble, helix bundle, calcium binding, metal binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, spindle: P62158
• Total number of polymer chains: 1
• Total formula weight: 16881.66

Authors

Gsponer, J.,Christodoulou, J.,Cavalli, A.,Bui, J.M.,Richter, B.,Dobson, C.M.,Vendruscolo, M. (deposition date: 2008-02-02, release date: 2008-06-10, Last modification date: 2024-05-29)

Primary citation

Gsponer, J.,Christodoulou, J.,Cavalli, A.,Bui, J.M.,Richter, B.,Dobson, C.M.,Vendruscolo, M.
A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction
Structure, 16:736-746, 2008

PubMed Abstract: We used nuclear magnetic resonance data to determine ensembles of conformations representing the structure and dynamics of calmodulin (CaM) in the calcium-bound state (Ca(2+)-CaM) and in the state bound to myosin light chain kinase (CaM-MLCK). These ensembles reveal that the Ca(2+)-CaM state includes a range of structures similar to those present when CaM is bound to MLCK. Detailed analysis of the ensembles demonstrates that correlated motions within the Ca(2+)-CaM state direct the structural fluctuations toward complex-like substates. This phenomenon enables initial ligation of MLCK at the C-terminal domain of CaM and induces a population shift among the substates accessible to the N-terminal domain, thus giving rise to the cooperativity associated with binding. Based on these results and the combination of modern free energy landscape theory with classical allostery models, we suggest that a coupled equilibrium shift mechanism controls the efficient binding of CaM to a wide range of ligands.

PubMed: 18462678
DOI: 10.1016/j.str.2008.02.017

Experimental method

SOLUTION NMR