Decoding the calcium signal: Structural insights into CBL-CIPK pathway in plants

Abstract

Calcium (Ca²⁺) signaling in plants is a major pathway in transducing diverse environmental stimuli. Calcineurin B-like proteins (CBLs) are one of the unique groups of Ca²⁺ sensors that transduce the Ca²⁺ signals by interacting with plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). In recent years, structure-function studies have provided key insights into the molecular basis of CBL-CIPK signaling and their interactions with the target proteins. The crystal structures of CBL2 and CBL4 have elucidated the architecture of non-canonical EF hands and provided the rationale for Ca²⁺ binding by CBLs. The molecular basis of interaction of the regulatory domain of CIPKs with CBLs has been established, providing rationale for CBL-mediated activation of CIPKs. The molecular mechanism of fine regulation of CIPK activity under non-stressed conditions and full activation under stressed conditions has been established using crystal structures of CIPK23 and CIPK24. Recently, high-resolution CryoEM structures of Arabidopsis and rice SOS1 led to a comprehensive understanding of its regulation and ion transport mechanism. In this review, major advances in understanding the structural basis of Ca²⁺ sensing by CBLs, molecular determinants of CIPK activation, and subsequent phosphorylation of target proteins are discussed. Remaining questions that need to be answered for a holistic understanding of the CBL-CIPK network are also discussed.