Autonomous protein folding units

Abstract

Publisher Summary This chapter presents the identification, characterization, and possible uses of autonomous folding units (AFUs), with special emphasis on studies aimed at understanding protein architecture and folding. Autonomous folding substructures, including even small subdomains may help reduce the complexity of conformational search by replacing the concerted folding of the entire polypeptide chain with smaller local folding reactions that subsequently assemble. It will be interesting to investigate the stepwise formation of a complex protein structure by determining the relative folding and assembly rates of subdomain AFUs. The observation that many AFUs consist of noncontinuous segments of the polypeptide chain, often corresponding to distant regions of the primary sequence, suggests that AFUs may provide an efficient mechanism for restricting conformational space by requiring collapse and compaction of distant stretches of the polypeptide chain at early stages of protein folding. The chapter focuses on the existing experimental data, such that they can be used as a benchmark for the future theoretical development of algorithms for predicting AFUs. In principle, negative results or regions that do not fold autonomously, can provide equally important information for understanding the principles of protein folding as those regions that are AFUs. AFUs can be used as fundamental building blocks in the design of proteins with novel functions.