Calcium in Signaling: Its Specificity and Vulnerabilities toward Biogenic and Abiogenic Metal Ions
- Resource Type
- Authors
- Todor Dudev; Cédric Grauffel; Carmay Lim
- Source
- The Journal of Physical Chemistry B. 125:10419-10431
- Subject
- chemistry.chemical_classification
Binding Sites
biology
Cations, Divalent
Chemistry
Metal ions in aqueous solution
chemistry.chemical_element
Calcium
Cofactor
Surfaces, Coatings and Films
Divalent
Cations
Second messenger system
Materials Chemistry
biology.protein
Biophysics
Physical and Theoretical Chemistry
Signal transduction
Intracellular
Binding selectivity
Signal Transduction
- Language
- ISSN
- 1520-5207
1520-6106
Divalent calcium ion (Ca2+) plays an indispensable role as a second messenger in a myriad of signal transduction processes. Of utmost importance for the faultless functioning of calcium-modulated signaling proteins is their binding selectivity of the native metal cation over rival biogenic/abiogenic metal ion contenders in the intra/extracellular fluids. In this Perspective, we summarize recent findings on the competition between the cognate Ca2+ and other biogenic or abiogenic divalent cations for binding to Ca2+-signaling proteins or organic cofactors. We describe the competition between the two most abundant intracellular biogenic metal ions (Mg2+ and Ca2+) for Ca2+-binding sites in signaling proteins, followed by the rivalry between native Ca2+ and "therapeutic" Li+ as well as "toxic" Pb2+. We delineate the key factors governing the rivalry between the native and non-native cations in proteins and highlight key implications for the biological performance of the respective proteins/organic cofactors.