Calcium Unified: Understanding How Calcium's Atomic Properties Impact Human Health

Calcium plays a major role in all cellular functions, and its regulation is important in all aspects of human health. This key role calcium plays in cell function can be traced to its unique molecular coordination geometry, which is often overlooked in understanding calcium function. In this review, we integrate calcium's ability to form various complexes with proteins and small molecules with its role as a key signaling atom. We argue that calcium's ability to vary its coordination structures, compared to magnesium's rigid geometry, explains its importance in biological functions. By examining calcium-mediated proteins, such as those containing EF-hand domains and those that assemble and stabilize the extracellular matrix in tissue organization, we demonstrate how calcium's varied geometric coordination serves as both a signaling molecule and a regulator of physiological homeostasis.