Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: two ways to promote

Mitsuhiko Ikura1, James B Ames

  • 1Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. mikura@uhnres.utoronto.ca

Insights

Calcium signaling relies on EF-hand proteins, like calmodulin, which change shape to interact with diverse cellular targets. This review explores how these calcium-binding proteins achieve functional diversity through molecular recognition.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Signaling

Background:

  • Calcium signaling pathways regulate crucial cellular events including gene transcription and ion transport.
  • These pathways involve calcium-binding proteins, collectively termed the calmodulin or EF-hand protein superfamily.
  • EF-hand proteins share structural similarities for calcium sensing but exhibit extraordinary functional diversity.

Purpose of the Study:

  • To review the molecular recognition activities of calmodulin superfamily proteins.
  • To elucidate the mechanisms by which these proteins control calcium (Ca2+) signaling processes.
  • To highlight similarities and variations in conformational responses to Ca2+ binding.

Main Methods:

  • Review of recent biochemical and structural studies.
  • Analysis of sequence homology and structural features.
  • Examination of protein-ligand interactions and conformational changes.

Main Results:

  • EF-hand proteins undergo significant conformational changes upon Ca2+ binding.
  • Calmodulin interacts with over 300 different proteins.
  • Neuronal calcium sensor and S100 protein families recognize distinct sets of target proteins.

Conclusions:

  • Despite conserved structural features, EF-hand proteins display remarkable functional diversity.
  • Molecular recognition mechanisms are key to the varied roles of calmodulin superfamily proteins in Ca2+ signaling.
  • Understanding these mechanisms is crucial for deciphering cellular event regulation.

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