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

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 8; p. 130819
• Main Authors: Bihani, Subhash Chandra, Tarushi, Srivastava, Ashish Kumar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2025
• Subjects: Abiotic stress; Arabidopsis; Arabidopsis - metabolism; Arabidopsis Proteins - chemistry; Arabidopsis Proteins - metabolism; calcium; Calcium - metabolism; Calcium Signaling; Calcium signature; Calcium-Binding Proteins - chemistry; Calcium-Binding Proteins - metabolism; CBL-CIPK complex; domain; Membrane transport; phosphorylation; Plant Proteins - chemistry; Plant Proteins - metabolism; Plants - metabolism; protein kinases; Protein Serine-Threonine Kinases - chemistry; Protein Serine-Threonine Kinases - metabolism; rice; SOS pathway; SOS pathway; CBL-CIPK complex; Abiotic stress; Membrane transport; Calcium signature
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130819

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. •EF-hand architecture of CBLs and Ca2+ binding.•C-terminal tail of CBL may be crucial for CBL-CIPK interaction.•Strucutral basis of CBL-CIPK interaction and CIPK activation.•High resolution structures of SOS1 from Arabidopsis and rice.