STRUCTURES OF CALMODULIN AND A FUNCTIONAL MYOSIN LIGHT-CHAIN KINASE IN THE ACTIVATED COMPLEX - A NEUTRON-SCATTERING STUDY

Calmodulin (CaM) is the major intracellular receptor for Ca2+ and is r esponsible for the Ca2+-dependent regulation of a wide variety of cell ular processes via interactions with a diverse array of target enzymes , Our current view of the structural basis for CaM enzyme activation i s based on biophysical studies of CaM complexed with small peptides th at model CaM-binding domains. A major concern with interpreting data f rom these structures in terms of target enzyme activation mechanisms i s that the larger enzyme structure might be expected to impose constra ints on CaM binding. Full understanding of the molecular mechanism for CaM-dependent enzyme activation requires additional structural inform ation on the interaction of CaM with functional enzymes, We have utili zed small-angle X-ray scattering and neutron scattering with contrast variation to obtain the first structural view of CaM complexed with a functional enzyme, an enzymatically active truncation mutant of skelet al muscle myosin light chain kinase (MLCK), Our data show that CaM und ergoes an unhindered conformational collapse upon binding MLCK and act ivates the enzyme by inducing a significant movement autoinhibitory se quences away from the surface of the catalytic core.