EF hand domains

EF-hand domains comprise two helices that are arranged roughly perpendicular to each other and connected by a loop. Most EF-hand units are paired to form a compact lobe, and often bind calcium ions with ligands located in the loop that connects the helices.

EF-hand Ca(2+)-binding proteins participate both in modulation of calcium signals and in direct transduction of an ionic signal into downstream biochemical events. The biochemical repetoire of EF-hand proteins is correlated with differential response to conformational changes caused by Ca(2+) binding. For example, calmodulin and calbindin have homologous EF-hand domains, yet they respond to calcium binding differently.[pm]

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modulator proteins

Modulator proteins regulate the activity of other proteins.

Calmodulin (Ca2+-regulated modulator protein, CaM) is a ubiquitous eukaryotic intracellular calcium receptor that regulates the biological activities of many cellular proteins and transmembrane ion transporters.

Calmodulin possess four EF-hand domains that alter conformation upon binding calcium ions. Calcium ions bind to the EF-loop region, shifting the relative positions of the EF-alpha helices. (The other group of proteins that depend on calcium ions for their function belong to the annexin family, which bind calcium and phospholipids). In the absence of calcium, the α-helices in the EF-hand motif of calmodulin are in the closed conformation, almost parallel to each other. When the intracellular calcium level rises, Ca2+ ions bind to calmodulin, causing calmodulin to open into a dumbell shape and increasing CaM's binding affinity. (Nine of CaM's 148 aa residues are methionines, and 8 of these 9 Met are directly involved in binding to all target peptides.) The open conformation Ca2+-calmodulin complex binds target proteins, initiating various signaling cascades. Over a hundred proteins are known to bind calmodulin (above left are three). Calmodulin is essential for cell-cycle progression through mitosis. []molecule of month[]

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