Essay 7- The Lac Operon
Year 2 Biomedical Science
“Discuss how the Escherichia coli lac operon is controlled.”
It is well known that bacterial do not express all their genes all the time to save resources. However the bacteria need to respond quickly to changes in the environment, these changes can be met by grouped genes which encode proteins that work together known as operons. E.coli is one of the most studied organisms worldwide, especially the study of its operons. E.coli can digest the sugar lactose, the genes which it needs to do this are inducible by the inducer, lactose. E.coli only needs the proteins to digest lactose when lactose is present. The lac operon consists of a few key genes for proteins, this proteins include: B-galactosidase, lactose permease and A-tranacetylase, which are translated from LacZ, LacY and LacA genes respectively.
B-galatosidase is an enzyme which cleaves lactose into galactose and glucose, it also catalyses the isomerisation of lactose to allolactose, a compound important in regulating the expression of the lac operon. Lactose permease Is a membrane bound proteins that brings lactose into the cell, and A-tranacetlyase rids the cell of toxic thiogalatosides that are taken up by the permease. In E.coli in a medium containing glucose, only a low concentration of each of these three proteins is produces as glucose is favoured over lactose. However in the presence of lactose and absence of glucose there are about 3,000 molecules of b-galactosidase per cell. The genes mentioned above, are transcribed into mRNA’s: these mRNA’s have short half-lives so the transcripts for these must be made continually in order for the enzymes to be produced. When lactose is no longer present production of mRNA is stopped and the mRNA already present is broken down so no more protein is made. On the lac operon there is also a lacl- gene present, this is the regulatory gene which is located close to the structural gene. Lacl- codes for a repressor molecule which controls the negative control of the lac operon system. The promoter for lacl- is weak so only a few repressor molecules are made, however these repressor molecules are made constitutively and bind to the operator. Once bound to the operator the lac repressor prevents transcription of mRNA as RNA polymerase cannot bind to the promoter when the repressor is bound to the operator (the operator modulates the expression of the gene). The lac repressor binds to the DNA sequence of the operator and overlaps the sequence to which the RNA polymerase binds. When the repressor is bound to the operator RNA polymerase cannot bind to the promoter and so no mRNA is produced and transcription cannot occur.
When E.coli grows in the presence of lactose as the only carbon source, some lactose is converted to allolactose by B-galatosidase. Allolactose binds to the lac repressor and changes its shape, the lac repressor loses its affinity to the operator, with no repressor bound to the operator, RNA polymerase is free to make polycistronic mRNA for lacZ, lacY and lacA which is translated by ribosomes into functional proteins. We now understand that the lac repressor protein exerts a negative control on the lac operon, preventing transcription, but there is also a positive control system which functions to turn on the expression of the operon. This system ensures that the operon is expressed at high levels only if lactose is the only carbon source, not if glucose Is present. More energy can be obtained from glucose than other sugar so cells do not waste energy on using lactose if glucose is present. if lactose is present and glucose is absent then a protein called Catabolite activator protein (CAP) binds to cAMP to form a CAP-cAMP complex, this complex is the positive regulator molecule. The CAP-Camp complex binds to the CAP site which is upstream of the site at which RNA polymerase binds to the promoter. CAP then helps RNA polymerase to bind and start transcription. However when glucose is present then it reduces the amount of cAMP in cells to be low. Adenylate cyclase makes cAMP, and when glucose is present Adenylate cyclase no longer works. This prevents the CAP-camp complex from forming. The operon has 4 different state: when no glucose and no lactose present, when no lactose but glucose present, when glucose and lactose both present and finally when there is only lactose.
In conclusion it is key to understand how the lac operon inducible system works within E.coli. Study of these operons leads to advancement in study of the human genome too, and applicable traits. Lac operon is a prime example of how bacterial ensure the conservancy of resources by turning off and on expression of genes dependent on need. As this gene regulation in bacteria is not fully understood, understanding how these genes are regulates helps us to understand how genes are regulated in higher organisms like humans.