Regulated unfolding: a basic principle of intraprotein signaling in modular proteins.
Modular proteins possess N-terminal sensor domains connected with different C-terminal output domains. Different output domains, for example, phosphodiesterases adenylyl cyclases, are regulated by identical N-terminal domains. Therefore, the mechanisms of intraprotein signaling share properties suitable to regulation of disparate output enzymes, which see the same signal but react differently. The common denominator is a reversible switch of folding/unfolding that connects sensor and output domains. In the inhibited state, output domains are restrained, whereas in the activated state domains are released to assemble according to intrinsic domain properties. We review recent work investigating the mechanism of intraprotein signaling and discuss how this signaling mechanism may have contributed to the evolutionary diversity of specific small molecule-binding domains without loss of regulatory properties.
Pharmazeutische Biochemie, Pharmazeutisches Institut, Universität Tübingen, 72076 Tübingen, Germany. Electronic address: joachim.schultz@uni-tuebingen.de.
Joachim E
JE
Schultz
Janani
J
Natarajan
D000262:Adenylyl Cyclases / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D002633:Chemotaxis; D000458:Cyanobacteria / Q000201:enzymology; D058767:Protein Unfolding; D015398:Signal Transduction
D001426:Bacterial Proteins; D000262:Adenylyl Cyclases
output domains; sensor domains; signal transduction