Structures of calmodulin and a functional myosin light chain kinase in the activated complex: A neutron scattering study

Joanna K. Krueger, Glenn A. Olah, Sue E. Rokop, Gang Zhi, James T. Stull, Jill Trewhella

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Calmodulin (CAM) is the major intracellular receptor for Ca2+ and is responsible for the Ca2+dependent regulation of a wide variety of cellular processes via interactions with a diverse array of target enzymes. Our current view of the structural basis for CaM enzyme activation is based on biophysical studies of CaM complexed with small peptides that model CaM- binding domains. A major concern with interpreting data from these structures in terms of target enzyme activation mechanisms is that the larger enzyme structure might be expected to impose constraints on CaM binding. Full understanding of the molecular mechanism for CaM-dependent enzyme activation requires additional structural information on the interaction of CaM with functional enzymes. We have utilized 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 skeletal muscle myosin light chain kinase (MLCK). Our data show that CaM undergoes an unhindered conformational collapse upon binding MLCK and activates the enzyme by inducing a significant movement of the kinase's CaM binding and autoinhibitory sequences away from the surface of the catalytic core.

Original languageEnglish (US)
Pages (from-to)6017-6023
Number of pages7
JournalBiochemistry
Volume36
Issue number20
DOIs
StatePublished - May 20 1997

ASJC Scopus subject areas

  • Biochemistry

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