Colicin Ia

Colicin Ia is a type of Colicin, a bacteriocin made by E. coli which acts against other nearby E. coli to kill them by forming a pore in the membrane, leading to depolarisation of the membrane which kills the cell.

Synthesis and releaseSynthesis and release

Colicin Ia is a 69kDa protein.

Mechanism of uptakeMechanism of uptake

spinqualitylabelsall models Structure showing the receptor binding domain of ColIa bound to its 70kDa outer membrane receptor (PDB entry 2hdi) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

The flexible N terminus of ColIa is responsible for binding to the colicin I receptor (Cir), which is a TonB-dependent transporter. Its normal function on E. coli is binding and transporting Fe³⁺ across the outer membrane, but is parasitized by colicins for their transport and entry. When ColIa binds to Cir it results in a big conformational change, resulting in Cir being open and exposed extracellularly, with the ColIa R-domain positioned directly above it, bound at approximately 45^o to the membrane. This results in the T and C domains remaining far above the membrane and away from the receptor. If Cir is indeed the molecule that transports ColIa across the membrane, this conformational change is that that would be required for penetration by the colicin.

The entry mechanism for ColIa into the periplasm after receptor binding is still unclear. The pair of α helices that separate the T and C domains from the R domain was suggested to allow ColIa to span the membrane, with the R domain being left outside the cell. The C domain is the only one expected to pass across the inner membrane and enter the cytoplasm. Alternatively the 45^o angle made with the membrane may allow the ColIa to search the surrounding regions for a co-transporter or other method of entry to the cell.

ColIa has been shown to transport cargo proteins on its N terminus across the lipid bilayer when it penetrates the target cell. This transport uses the voltage across the bilayer to bring the folded proteins across the membrane.

Killing ActivitiesKilling Activities

The channel forming domain, once it has translocated across the periplasmic space, inserts into the inner membrane of the target E. coli and forms a voltage-dependent ion channel.