タンパク質配列に隠された機能ペプチド、クリプタイドの発見とそれらの生理的機能

抄録

Peptidergic hormones and neurotransmitters are known to be produced by the specific cleavage of their precursor proteins that per se have no biological functions. The neutrophil-activating peptides we recently identified, however, are the peptides cleaved from mitochondrial proteins by proteolysis [1,2]. Therefore, we designated functional peptides hidden in protein sequences "cryptides" and named them "mitocryptides" because they are hidden in mitochodorial protein sequences [3]. Some of these peptides activate Gi type of G proteins directly, and neutrophils are suggested to be stimulated by the direct (i.e., not via GPCRs) activation of G proteins. These peptides had features, in common, in their distributions of charged and hydrophobic amino acid residues, but homologies in their primary structures were not apparent. In the present study, we predicted functional cryptic peptides that activate G proteins, based on the distribution of charged and hydrophobic residues. Receptors for these peptides were also investigated by the direct cross-linking experiments between peptides and their targeted proteins. The finding of functional cryptic peptides is expected to lead to the identification of novel signaling mechanisms where such peptides are involved in the regulation of bio-functions
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[1] Mukai, H., Hokari, Y., Seki, T., Nakano, H., Takao, T., Shimonishi, Y., Nishi, Y., and Munekata, E. (2001) Peptides: The Wave of the Future, 2001, 1014. [2] Mukai, H., Matsuo. Y., Kamijo, R., and Wakamatsu, K. (2004) Peptide Revolution: Genomics, Proteomics & Therapeutics, 2003, 553. [3] Ueki, N., Someya, K., Matsuo, Y., Wakamatsu, K., and Mukai, H. (2007) Biopolymers (Pep. Sci.), 88, 190.