42. Localized increases in the cytosolic level of free Ca²⁺ arecritical to its function as second messenger. Calmodulin,a small cytosolic protein, mediates many cellular effectsof Ca²⁺. Which of the following is NOT CORRECT forCa²⁺ calmodulin interaction?
(1) Each calmodulin molecule binds six Ca²⁺ions in acooperative fashion.
(2) Binding of Ca²⁺ causes calmodulin to undergo aconformationalchange leading to activecalmodulin.
(3) Since binding of Ca²⁺ is cooperative, a small changein the level of cytosolic Ca²⁺leads to a large changein the level of active calmodulin.
(4) One of the many enzymes activated by Ca²⁺calmodulin is CAMP phosphodiesterase, whichdegrades CAMP and links Ca²⁺ and CAMP signaling.

Calcium-Calmodulin Interaction: Clarifying Key Facts

Introduction

Calmodulin is a small, ubiquitous cytosolic protein that serves as a major transducer of intracellular calcium signals. By binding calcium ions (Ca2+2+), calmodulin undergoes conformational changes that enable it to regulate a wide array of cellular functions through interaction with diverse target proteins.

Correct Facts about Ca2+2+-Calmodulin Interaction

1. Calmodulin Binding Sites: Each calmodulin molecule contains four EF-hand motifs (helix-loop-helix structures) that bind calcium ions. Overall, calmodulin binds four Ca2+2+ ions, not six.

2. Cooperative Binding: Calcium binding to calmodulin is cooperative; the affinity for Ca2+2+ increases as more calcium ions bind, allowing calmodulin to respond sensitively to small changes in intracellular calcium concentration.

3. Conformational Change: Binding of Ca2+2+ triggers a large conformational change in calmodulin, exposing hydrophobic surfaces essential for interaction with target enzymes, effectively converting calmodulin into its active form.

4. Activation of Target Enzymes: Among the enzymes activated by Ca2+2+-calmodulin is phosphodiesterase that specifically degrades cAMP, thereby linking Ca2+2+ signaling to modulation of the cAMP pathway.

Evaluating the Given Statements

Conclusion

The INCORRECT statement is (1) as calmodulin binds four, not six, calcium ions. All other statements accurately reflect the biochemical and functional properties of calcium-calmodulin interaction and signaling.