ABC Transporters
ABC proteins are a large group of proteins with ~80 genes in human in E. coli. They participate in most cellular functions, functioning mostly (but not exclusively) as transporters. No matter what their physiological function is, ABC transporters share common elements of primary, secondary, and tertiary structure. For some time, these similarities between ABC transporters of different functions prompted the ABC community to assume that these transporters also share a common mechanism.
We now realize that this is not true.
Through studies of the mechanism of action of the vitamin B12 transporter BtuCD-F we found that its mechanism of action is completely different from what has been described for other transporters.
We believe that this is not coincidental, and that the special mechanism of BtuCD-F is exactly what makes it a fine-tuned machine for scavenging a rare (yet essential) molecule such as vitamin B12.
The catalytic transport cycle of the vitamin B12 transporter BtuCD-F:
The first two steps of the transport cycle, substrate binding and its translocation into the cell are fast, energy independent processes. Only after substrate is imported the system requires energy to reset itself. In the absence of substrate the system will keep hydrolyzing ATP, poised for action. This mechanism is specifically adapted to scavenging a rare element such as vitamin B12.
When hunting for a rare element, you want to make sure that when you encounter your target you’ll catch it and bring it in. E. coli needs only a few molecules of vitamin B12, so the transport needs not be very fast or highly processive. But it must be of high affinity, and it must be successful when it gets a chance.
This approach will not work for an importer of a consumable metabolite (a carbon source for example). Carbon sources are not that rare, so you don’t need such a high affinity. On the other hand, just a few molecules will not do, especially when you’re a hungry bacteria. These are just examples as to why we think each transport system needs to be mechanistically adapted to its specific function.
Mechanistic adaptations in ABC transporters
Our goal is to understand the relation between the molecular mechanism of a given system and its physiological role.
Through structural and phylogenetic classification we now know that there are some 20 different groups of ABC transporters.
Of these, ~4-5 systems have been described mechanistically, to varying extents. So much is yet to be discovered.
We are currently in the process of establishing the experimental platforms that will allow us to directly compare, side-by-side, transporters that have very different functions. We work on nucleotide transporters, transporters of rare metals, transporters of vitamins, metabolites, signaling molecules…..
We believe we have seen just the tip of the iceberg, and that fascinating mechanistic adaptations await to be discovered.