Iron Transport and the Ferric Uptake Regulator System By Pranav Khemka

Iron Transport and the Iron Transport and the Ferric Uptake Regulator Ferric Uptake Regulator SystemSystemBy Pranav Khemka

E. coliE. coliGram negative: bacterial cell wall

lacks a thick layer of peptidoglycanRod shaped and generally harmless

and located in the lower intestine

http://asymptotia.com/wp-images/2008/08/e_coli.jpg

IronIronIron is an essential component in

biological systemsUsed as a cofactor for many

reactionsBut, reactivity of iron can cause

side reactions causing the production of peroxides causing cell lysis

Must be carefully transported

http://www.google.ca/imgres?q=Fe2%2B&um=1&hl=en&biw=1280&bih=597&tbm=isch&tbnid=0kqmWYu2uKxGCM:&imgrefurl=http://www.automation.com/resources-tools/articles-white-papers/instrumentation-test-measurement/innovations-in-corrosion-monitoring&docid=GbER-UUzdEo4MM&w=389&h=288&ei=1whtTuSQGcPt0gGgiPH5Cw&zoom=1&iact=rc&dur=295&page=1&tbnh=143&tbnw=193&start=0&ndsp=17&ved=1t:429,r:4,s:0&tx=54&ty=58

Iron Uptake SystemsIron Uptake SystemsIron uptake system are

evolutionarily relatedIron can be transported into a

cell by directly binding to iron, iron binding proteins, and iron chelators

Iron uptake is under the direct influence of Fur

Primary mode of transport: Primary mode of transport: Iron ChelatorsIron ChelatorsSiderophores:

◦Name: Enterobactin or Enterochelin◦Produced within E. coli during low

iron stress and transported to the outer membrane

◦Role: find iron in the environment and make it available in the cell

Source- Enterobactin: An archetype for microbial iron transport

Enterobactin siderophore

Enterobactin Iron Acquisition Enterobactin Iron Acquisition ProcessProcessEnterobactin binds to iron and a

change of confirmation occurs in the siderophore

The general mechanism is initiation when FeEnt binds to a receptor protein on the E.coli cell surface (rate limiting step)

Transport of the complex requires active transport ending with iron release within the cellEnterobactin bound to iron (FeEnt)


Continued…Continued…The membrane protein

receptor/channel FepA binds to FeEnt and allows it to enter through the outer membrane (OM)

Once through the OM FeEnt is translocated into the cytoplasm via the ATP cassette transporter


Structural representation of FepA. PDB ID: 1FEB

ATP Cassette TransporterATP Cassette TransporterThis form of transport is conserved

between species1) FeEnt binds to the periplasmic binding

protein FepB2) FepB with FeEnt is transported to

cytoplasmic membrane spanning proteins

The structure of FepB has not been determined


Transport Pathway Diagram

Continued…Continued…2a) FepB FeEnt complex interacts with

the cytoplasmic membrane (CM) spanning proteins FepD and FepG

3) Transport of FeEnt through the cytoplasmic membrane occurs through ATP hydrolysis via the ATP binding protein FepC

4) Ferric siderophore crosses CM5) Iron cleaved and used for metabolic

processes


Transport Pathway Diagram

Regulation. A bit on FurRegulation. A bit on FurMost iron responsive genes are

directly influenced by the Ferric Uptake Regulator (FUR) repressor

Likewise, Fur is capable of controlling its own synthesis

Little is known about the structure of Fur

Upon binding to iron (Fe2+) fur will act like a repressor

The Fur gene and the Fur The Fur gene and the Fur proteinproteinFur upon binding with iron is able

to sit on the DNA template and act like a repressor

Prevents RNA polymerase to function

Source- http://ecocyc.org/ECOLI/NEW-IMAGE?type=GENE&object=EG10359

Fur gene and fur repression

What happensWhat happensWhen fur production is

repressed… enough iron has been transported into the cell for it to use for various activities

When intracellular iron levels are low Fe2+ is cleaved from the Fur repressor and the process repeats

ReferencesReferences 1) Clarke, T.E., Tari, L.W., & Vogel, H.J. (2001) Structural

Biology of Bacterial Iron Uptake System. Current Topics in Medicinal Chemistry. 1. 7 – 30.

2) Raymond, K.N., Dertz, E.A., & Kim, S.S. (2003). Enterobactin: An archetype for microbial iron transport. PNAS. 100 (7). 3584 – 3588.

3) EcoCyc. (2011). Escherichia coli K-12 substr. MG1655 Polypeptide: Fur. http://ecocyc.org/ECOLI/NEW-IMAGE?type=GENE&object=EG10359. Accessed on September 11, 2011.

4) Escolar, L., Pérez-Martín, , & Lorenzo,V.d. (1999). Opening the Iron Box: Transcriptional Metalloregulation by the Fur Protein. Journal of Bacteriology. 181(20). 6223 – 6229.

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Iron Transport and the Ferric Uptake Regulator System By Pranav Khemka