Putting on the Finishing Touches Quiz

Answer: Ubiquitin

Ubiquitin is a 9kDa protein that is attached to lysine residues of proteins that require degradation. This process is mediated by a group of proteins called the ubiquitin ligases, which are given the alpha-numeric name E3. After ubiquitylation takes place, the marked protein is recognised by a structure in the cell called the proteasome, which degrades the protein into small peptides.

This process is important in maintaining proper cell functionality. Damaged proteins are often characterised by exposed hydrophobic regions, which results in protein aggregation and the formation of plaques which are characteristic of disorders such as Alzheimer's.

Answer: Vitamin K

Vitamin K-dependent enzymes facilitate the carboxylation of glutamate residues on the protein known as prothrombin. This event is necessary for the cleavage of prothrombin into thrombin, which can then cleave fibrinogen to form insoluble fibrin, which helps to stop blood flow at areas of damage.

Answer: Collagen

Collagen is a major structural protein in our bodies that requires the assembly of a triple helix formation. Hydroxylation of the proline residues of collagen (forming hydroxyproline) is necessary for the formation of this triple helix. Furthermore, hydroxylation of lysine residues in collagen then allows these triple-helical strands to become cross-linked to other collagen triple helices, thus providing strength. The requirement of vitamin C in proper collagen formation is seen in cases of scurvy, when skin becomes weak.

Hydroxylation is also important in the maintenance of a protein called hypoxia inducible factor 1 (HIF1). In normal circumstances, HIF1 is synthesised and is hydroxylated, allowing it to then be ubiquitylated and therefore degraded. In times where oxygen is scarce, however, HIF1 is not hydroxylated or degraded and so can promote the formation of blood vessels to the hypoxic tissue.

Answer: Histones

Histones are complexes of proteins and, with DNA, make up the material known as chromatin. Histones have "tails" which are highly basic, meaning that they are positively charged and so can associate with the negatively charged DNA. Lysine contributes to the positive charge of the histone tails, but are neutralised by addition of acetyl groups (a process known as acetylation), therefore allowing the DNA to become available and for gene expression to occur.

Acetylation is also important in other, non-histone proteins. Acetylation occurs at lysine residues - the same residues that are ubiquitylated. Acetylation therefore prevents ubiquitylation and degradation. Acetylation can therefore be seen as a stabilising modification to proteins.

Answer: Methylation

Methylation can occur at both the DNA and protein constituents of chromatin, and can be either inhibitory or activating of gene expression. A fine balance therefore has to be maintained to allow proper cell functionality. It has been found that cancer is often associated with a general under-methylation, but that hypermethylation occurs at specific positions which effectively silence the genes. Genes that are silenced in this so called "promoter hypermethylation" includes that which codes for E-cadherin - a protein important in preventing metastasis. For more information on the molecular basis of cancer, I invite you to play my quiz "Cancer is an Inevitability for the Immortal".

Answer: Kinases

There are thought to be over 500 different kinases encoded by the human genome. The complexity and subtlety with which kinases influence cellular activity is seen by the fact that they can be both inhibitory and activating, as well as both stabilising and destabilising.

The effect of the phosphate group often depends on the residue which is phosphorylated and the context/environment in which the phosphorylation takes place.

Answer: Glycosylation

Glycosylation is a common modification on proteins that are either membrane-bound or secreted. Proteins that form part of the extracellular matrix (which surrounds the cells) are often highly glycosylated. This high degree of glycosylation provides shock absorbance, as well as a reservoir for several factors key to cell growth and repair, and which are released upon damage to the extracellular matrix. One example of glycosylated proteins is mucins, which form mucus. For more information on mucus, I invite players to play my quiz "S'Not Just Sticky Mess".

Answer: Disulphide bridges

The existence of disulphide bridges helped to resolve one of the greatest paradoxes in biochemistry. It was known that proteins folded rapidly into their correct shapes after being synthesised, but it was not known how this could happen with so many possible folding combinations.

This is the Levinthal Paradox. The formation of disulphide bonds greatly reduces the number of possible folding combinations and so narrows down the number of routes a protein can take, thus helping to resolve the Levinthal Paradox.

Answer: The cell membrane

Prenylation often acts as an anchor for proteins at the plasma membrane. Since Ras is important in transducing signals from outside to inside of the cell, it is logical that it should be localised at the boundary between these two environments. Ras is located next to proteins called receptor tyrosine kinases, which, when stimulated, recruit proteins which activate Ras. Active Ras is involved in inducing cell proliferation, survival, and migration, amongst other things.

Answer: Zymogens

Cells such as those found in the pancreas are responsible for synthesising many enzymes which are involved in degrading food which passes through our digestive system. Prior to their secretion, the enzymes exist in an inactive state which prevents damage to the cell itself. Proteins other than enzymes also exist in inactive ("pro-") states prior to proteolytic cleavage, such as insulin.