Extremely charged coral protein AGARP regulates calcium carbonate growth through liquid phase separation

Abstract

AbstractBiomineralizationviathe non-classical crystallization pathway is postulated to involve a transient liquid phase of calcium carbonate formed in the presence of polymers. In the context of coral biocalcification, these polymers may include coral acid-rich proteins (CARPs), secreted into the skeletal organic matrix. However, direct evidence for the existence of this liquid phase with proteins is lacking. Here we report the properties of the intrinsically disordered aspartic and glutamic acid-rich protein (AGARP), which is the first CARP cloned from one of the most studied scleractinian coral of the Great Barrier Reef,Acropora millepora, a model species for biomineralization and ecological studies. We show that AGARP can significantly influence early stages of CaCO3nucleation and crystal growth through liquid-liquid phase separation. Consequently, we introduce the concept of a biologically relevant crystallization precursor, a liquid protein-calcium condensate composed of CARP molecules and Ca2+ions, that forms as a result of liquid phase separation in a viscous, crowded environment. Our work bridges the gap between the liquid phase separation and biomineralization research.