Identification and Structure-Activity Studies of Novel Cryptides Hidden in Mitochondrial Proteins

摘要

Neutrophils are known to involve innate immunity, but endogenous factors which induce acute transmigration and activation of them have not been well elucidated so far. We therefore explored such unknown factors and recently identified two novel neutrophil-activating peptides, mitocryptide-1 (MCT-1) and -2 (MCT-2), which were derived from mitochondrial cytochrome c oxidase and cytochrome b, respectively [1-5]. We also found the presence of many neutrophil-activating peptides presumably derived from various mitochondrial proteins other than MCT-1 and MCT-2, indicating that neutrophils are regulated by many unidentified mitochondrial protein derived peptides [4,5]. We named such functional peptides hidden in protein structures "cryptides" [3-7]. After our discovery, the evidence has been accumulated that fragmented peptides derived from various functional proteins have variety of biological functions that are distinct from the roles of their mother proteins, and the presence of non-classical bioactive peptides derived from functional proteins, including cytosolic ones, is widely recognized [6-10]. In addition, specific receptor molecules and cellular signaling mechanisms for those cryptides are going to be characterized [6-9]. Here, we report our attempt to identify novel neutrophil-activating cryptides hidden in various mitochondrial proteins. We also communicate structure-activity relationships of these cryptides on the activation of neutrophilic differentiated HL-60 cells.