Domain architectures
Now that we got parts pumping through the pipeline, it’s time to take a step back and reflect once again on one of our favorite themes of the summer: the modularity of protein domains. I just posted a depiction of a familiar protein, PI3K, represented not as a crystal structure or as a cartoon blob, but with respect to its DOMAIN ARCHITECTURE. By domain, I mean the smallest functional units of a protein, and by architecture I mean the arrangement/organization of the domains within the protein as a whole. This representation is the way a protein looks to a bioinformaticist, a scientist who uses computer algorithms to search DNA, RNA or protein sequences to look for patterns, evolutionary conservation, and other interesting sequence-encoded functional hallmarks. Internet-based tools such as the Simple Modular ARchitecture Tool (SMART) make it easy to identify domains in your protein of interest, as well as allow you to search across evolution for proteins that contain your domain of interest (or combinations of domains).
Take another look at the domain architecture of PI3K. You can see that even PI3K has more domains in the full protein than just the catalytic kinase domain. What do you think these other domains might do?
When you start to think about new parts you may want to design, one good way is to search for proteins in nature that have a certain domain you are interested in, and then take the domain from these natural proteins and express them in your synthetic circuit.