Colicin Ia: Difference between revisions
Michal Harel (talk | contribs) No edit summary |
|||
| (10 intermediate revisions by 3 users not shown) | |||
| Line 1: | Line 1: | ||
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 voltage-dependent channel in the inner membrane of the cells that it targets. | <StructureSection load='1cii' size='450' side='right' scene='' caption='E. coli colicin Ia (PDB code [[1cii]])'> | ||
'''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 voltage-dependent channel in the inner membrane of the cells that it targets. | |||
==Synthesis and release== | ==Synthesis and release== | ||
| Line 8: | Line 10: | ||
==Mechanism of uptake== | ==Mechanism of uptake== | ||
<scene name=Colicin_Ia/Coliarcir/1>Structure showing the receptor binding domain of ColIa bound to its 70kDa outer membrane receptor</scene> (PDB entry [[2hdi]]). | |||
The flexible<ref> PMID: 15452437 </ref> N terminus of ColIa is responsible for binding to the colicin I receptor (Cir), with high affinity (K<sub>assoc</sub>=1x10<sup>10</sup>M<sup>-1</sup><ref> PMID: 4561939 </ref>). Cir is a 22-stranded plugged β barrel TonB-dependent transporter. Its normal function on ''E. coli'' is binding and transporting Fe<sup>3+</sup> 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<sup>o</sup> 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<ref> PMID: 17464289 </ref>. ColIa molecules with the receptor binding domain deleted are still able to enter cells, although less effectively, as Cir weakly binds to the translocation domain as well as the receptor binding domain<ref> PMID: 19919671 </ref>. | |||
The flexible<ref> PMID: 15452437 </ref> N terminus of ColIa is responsible for binding to the colicin I receptor (Cir), | |||
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<ref> PMID: 9729746 </ref>. Alternatively the 45<sup>o</sup> 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. For killing by ColIa to be successful, Cir requires a functional [[TonB]] box sequence, as does ColIa, which implies that an interaction with TonB is required for uptake of ColIa<ref> PMID: 17464289 </ref>. | 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<ref> PMID: 9729746 </ref>. Alternatively the 45<sup>o</sup> 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. For killing by ColIa to be successful, Cir requires a functional [[TonB]] box sequence, as does ColIa, which implies that an interaction with TonB is required for uptake of ColIa<ref> PMID: 17464289 </ref>. | ||
| Line 27: | Line 28: | ||
Insertion of ColIa into the lipid membrane triggers a series of conformational change across the whole of ColIa to form the ion channel<ref> PMID: 10845238 </ref>, probably through a series of intermediates. While a monomer of ColIa in the membrane is sufficient to form the channel and kill the cell, studies have shown that the channel, when enough molecules are present, exists as a multimer with a larger pore diameter<ref> PMID: 9729746 </ref><ref> PMID: 19357078 </ref>. | Insertion of ColIa into the lipid membrane triggers a series of conformational change across the whole of ColIa to form the ion channel<ref> PMID: 10845238 </ref>, probably through a series of intermediates. While a monomer of ColIa in the membrane is sufficient to form the channel and kill the cell, studies have shown that the channel, when enough molecules are present, exists as a multimer with a larger pore diameter<ref> PMID: 9729746 </ref><ref> PMID: 19357078 </ref>. | ||
Once the pore has inserted into the membrane and is functioning fully, it inhibits the active transport of a number of molecules, primarily proline, thiomethyl-β-D-galactoside, and K<sup>+</sup> ions. Not only does it prevent their uptake, it can also trigger the rapid release of the molecules. It also inhibits succinate uptake, which accounts for the inhibition of respiration observed in targeted cells, and has an effect on the uptake of glycerol<ref> PMID: 1091634 </ref>. | Once the pore has inserted into the membrane and is functioning fully, it inhibits the active transport of a number of molecules, primarily proline, thiomethyl-β-D-galactoside, and K<sup>+</sup> ions. Not only does it prevent their uptake, it can also trigger the rapid release of the molecules. It also inhibits succinate uptake, which accounts for the inhibition of respiration observed in targeted cells, and has an effect on the uptake of glycerol<ref> PMID: 1091634 </ref>. All of this leads to an uncoupling of electron transport from active transport, and affects energy metabolism with its interference with the membrane, leading to a depolarisation of the membrane<ref> PMID: 388932 </ref><ref> PMID: 26912 </ref><ref> PMID: 779829 </ref>. | ||
</StructureSection> | |||
==References== | ==References== | ||
<references/> | <references/> | ||