Introdution to our Research

Experimental approaches to extracting information from amino-acid sequences

What are the basic elements that determine the functions of a protein as a molecular machine? Let us use the analogy of a mechanical device. Many of you who are reading this may have had an embarrassing childhood experience in which, after having disassembled a device, you could not return the parts to their proper locations. We have an innate desire to break down an apparatus into its parts to see how it works. What are the building blocks of the protein function? The answer is: we do not yet know.
　We have not yet elucidated the most basic concept in the science of protein function: the fundamental parts that constitute protein functionality. Here, we define a “part” as the smallest indivisible component of the machinery that has a distinct role. The combination of those parts enables higher-order functionality.

Over the course of evolution, organisms have conserved particular amino-acid sequences, and these so-called ‘domains’ are indivisible segments. It should be theoretically possible to identify all the indivisible domains by following them over the entire course of evolution. However, we adopt a more practical approach: we conduct genetic engineering studies to simulate a hypothetical evolutionary process, and identify indivisible domains. Consequently, we found that genetically engineered proteins contained dozens of indivisible segments, each consisting of a few to around 10 amino acids. We termed those segments “functional elements,” based on the assumption that they are the functional building blocks of the protein. Interestingly, we found that functionally indivisible segments did not necessarily coincide with structurally indivisible segments. We are currently investigating whether those functional elements are present in common proteins, as well as their specific roles. The goals of our research include understanding the guiding principles of protein evolution and proposing genetic methods for the design of new functional proteins.