Kalmoduliini

Kalmoduliini, known in English as calmodulin, is a small, highly conserved calcium-binding messenger protein found in all eukaryotic cells. It translates fluctuations in intracellular calcium into varied cellular responses by modulating the activity of numerous target proteins. Through this role, kalmoduliini influences muscle contraction, neurotransmitter release, enzyme activity, gene expression, and cell-cycle progression.

Structurally, kalmoduliini consists of 148 amino acids arranged into two globular lobes (N-terminal and C-terminal) connected by a flexible linker. Each lobe contains two EF-hand calcium-binding motifs, giving a total of four calcium-binding sites. In the absence of calcium, kalmoduliini adopts a compact conformation; binding Ca2+ induces a conformational change that exposes hydrophobic surfaces, enabling interactions with diverse target peptides and proteins.

Functionally, kalmoduliini acts as a calcium sensor and signal transducer. It activates or modulates enzymes and other proteins, including calcium/calmodulin-dependent kinases (CaMKs), calcineurin, myosin light-chain kinases, and various ion channels and phosphodiesterases. Through these interactions, it integrates calcium signals with cellular processes such as metabolism, secretion, and cytoskeletal dynamics.

Genetically, kalmoduliini is encoded by three highly similar genes in humans: CALM1, CALM2, and CALM3, each producing multiple nearly identical protein isoforms. The protein is broadly expressed and essential for viability, reflecting its central role in calcium signaling across tissues and organisms.

Clinical relevance includes calmodulin-related disorders, sometimes termed calmodulinopathies, where mutations in CALM genes disrupt calcium signaling and can contribute to cardiac arrhythmias such as long QT syndrome and, in rare cases, sudden infant death. Research continues to elucidate kalmoduliinin interactions and therapeutic implications.