Lysine
Amino acids are organic molecules, the monomers of proteins that contain both amino and carboxyl groups. Proteins of a cell mostly contain 20 types of amino acids that differ in the side chain known as R group. Therefore, the properties of the amino acid in protein fully depend on the characteristics of the side chains.
Lysine is an essential amino acid, that means it cannot be synthetized in the human organism. The side chain of the lysine molecule contains an additional amino group attached to the carbon skeleton. Because of the positive charge in the side chain, the charge of the molecule is also positive, making it hydrophobic and basic amino acid. The conclusion can be made that in the folded protein at a cell PH that is close to 7, lysine will contribute to the positive charge of the protein. Moreover, in aquatic or other polar solution, lysine will most probably be located on the outer surface of the molecule.
Levels of protein structure
In the sequence of amino acids the side chains interact with each other and with the surrounding molecules and solutions, so the size, charge, hydrophobicity or hydrophilicity and the other chemical properties of the side chains contribute to the formation of the protein structure with the lowest possible energy. In turn, the structure of the molecule determines its functions. For instance, the conformation of the molecule affects its interaction with other molecules that is highly important for enzymes and antibodies.
There are four levels of the protein structure in cells:
The first level or primary structure is the sequence of amino acids. This level is formed in the course of translation, when ribosome synthesizes the new polypeptide chain on the basis of messenger RNA. The structure is formed by amide linkages between the amino acids that are called peptide bonds.
The interactions between amino acids in the sequence form the second level or the secondary structure. The oxygen, nitrogen and hydrogen atoms in the polypeptide backbone of the sequence can form numerous hydrogen bonds, that results in the arrangement of the repeated fragments and formation of a three-dimensional folding pattern. Two most common types of the secondary structure are alpha-helix and beta-pleated sheet. The first type is stabilized by hydrogen bonding between every fourth peptide bond and looks like a cylinder-like twisted chain. This type is common for the transmembrane proteins, since it is the most energetically effective way for the protein to cross the membrane. The second type is stabilized by hydrogen bonding between the atoms in chains that lay side-to-side. It can form between two different chains that run in the same direction or between the parts of the same chain that goes back and forth upon itself. These chains are called parallel and antiparallel respectively. Beta-pleated sheet is common for globular and fibrous proteins.
The complex of different secondary structures of the protein forms the third level or the tertiary structure. This full three-dimensional structure mostly depends on the properties and non-covalent interactions of the side chains of the molecule. It is stabilized with such interactions, as electrostatic attractions or ionic bonds, hydrogen bonds between the atoms in the side chains, van der Waals attractions, hydrophobic attractions and covalent disulfide bonds or bridges between cysteine residues.
The last level or the quaternary structure can be observed when two or more peptide chains form a complex structure with specific shape and functions. These chains are called subunits of the protein and are held together with the help of both covalent and non-covalent bonding. The complex might also include a non-protein part. The typical examples of the quaternary structure are globular and fibrous proteins.
Formation of Peptide Bonds
Proteins are polymers synthesized from amino acid monomers. Amide linkage or peptide bond is formed between the carboxyl group of the first amino acid and the amino group of the following one. Dehydration reaction takes place and one water molecule is released. On ribosomes this reaction repeats for hundreds of times till the full sequence with free amino and carboxyl ends is synthesized.
Break of Peptide Bonds
The opposite reaction takes place in the course of protein degradation. The hydrolysis of peptide bonds occurs when the hydroxyl group, present in aquatic solution is attached to the carboxyl group of the amino acid, which forms the bond, and the hydrogen ion or proton is attached to the amino group of another amino acid. The process might occur spontaneously.
Forces That Stabilize Protein’s Tertiary Structure
As mentioned above, a protein’s territory structure is stabilized by covalent disulfide bridges, non-covalent ionic bonds, hydrogen bonds, van der Waals attractions and hydrophobic attractions.
Disulfide bonds are formed between two thiol groups cysteine residues in the course of their oxidation. This is the strongest bond of all the abovementioned. Ionic bonds or electrostatic attractions form between partially or fully charged molecules with the opposite charge. Hydrogen bonds form when electropositive hydrogen atom is covalently bonded to electronegative atom, but is partially shared with another electronegative atom. These forces are weak, but because of the great number of such bonds, their contribution to the shape of the molecule is significant. Van der Waals attractions appear between the non-polar molecules that have regions with positive and negative charge due to fluctuations of the electronic cloud. These forces are weak and might be observed only when the molecules are close together. Hydrophobic attractions bring together hydrophobic regions of the molecules together to reduce breaking of hydrogen bonds between the water molecules in solution, therefore, reduce the energy of the protein molecule.
Protein Misfolding and Aggregation in BSE
A prion is a misfolded protein that can negatively affect normal cell proteins, therefore, can be treated like infectious agent. Bovine spongiform encephalopathy or mad cow disease is a neurodegenerative disease that affects the cellular prion protein (PrPC) – a membrane associated protein, which functions still remain unknown (Kupfer, Hinrichs & Groschup, 2009). When the isoform of this protein – the prion PrPSc - invades the cell, it affects the conformation of the normal cellular protein. It contributes to destabilization of alpha-helixes in the protein, therefore, completely changes its structure. In turn that leads to a simultaneous formation of beta-sheets. Proteins with changes secondary structure connect with each other, forming hydrogen bonds between such beta-sheets and starting the aggregation of the proteins. According to Chaudhuri & Paul (2006), such aggregations are protease resistant and insoluble. They form amyloid fibrils in the central nervous system that contributes to the neurodegradation responsible for all the further symptoms of the disease.
Chaperones are the proteins that are responsible for the folding of all the proteins of a cell. On the basis of the secondary structure a protein can form several alternative tertiary structures, only one of which is the needed structure. Chaperones create the conditions needed for a protein to achieve the right conformation. Another function of chaperones is recognition of abnormally folded proteins and the initiation of their degradation. In normal cells the aggregates of any proteins are quickly removed, but in cells infected by the prion PrPSc the infectious agents act like chaperones, choosing the folding direction and compete with normal chaperons. Moreover, the formed aggregates are stable and protease resistant, therefore, cannot be easily removed with the help of ubiquitin-dependent degradation.
Prions can be found in any part of the infected organism, including blood. Moreover, they are heat-resistant; therefore, the meat of the animal remains infected even after the standard heat treatment. That is why the most appropriate method to prevent the disease is to forbid the recycling of bovine tissues that have the possibility to be infected. The immediate measures should be taken in each case of the disease recognition, including the complete destruction of the infected materials using the temperatures over 700° C.
References
Campbell, N. (2008). Biology (8st ed.). San Francisco: Pearson/Benjamin Cummings.
Chaudhuri, T., & Paul, S. (2006). Protein-misfolding diseases and chaperone-based therapeutic approaches. FEBS Journal, 273(7), 1331--1349.
Jones, G., & Tuite, M. (2005). Chaperoning prions: the cellular machinery for propagating an infectious protein?. Bioessays, 27(8), 823--832.
Kupfer, L., Hinrichs, W., & Groschup, M. (2009). Prion protein misfolding. Current Molecular Medicine, 9(7), 826--835.
Wilson, J., & Hunt, T. (2008). Molecular biology of the cell (5ер ed.). New York: Garland Science.
