This is my second reflection on proteins which I will also be using as a video review of a video by BiochemJM on Youtube.
Here’s the link: http://www.youtube.com/watch?v=ZWLNkEJloJA
His videos are a good source of Biochemistry related material.
This review will focus on proteins. Basically there are four main structures associated with proteins being Primary structures, secondary structures, Quaternary structures and Tertiary structures.
Image obtained from: http://4.bp.blogspot.com/_ee2yOd0wTkk/TLfmPbTNEXI/AAAAAAAAAAs/eyaXy8fKMwg/s1600/0048.gif
In the primary, secondary and tertiary structures the main structures are the single polypeptide chains. There is increased folding no folding in the chain from primary to some folding in the secondary to more folding in the tertiary.
All proteins will have a primary and secondary structure but only some will develop tertiary structures and fewer will form quaternary structures. The folding relies on the protein and its function.
The primary level of structure is a linear sequence of amino acids joined together by peptide bonds. This sequence is determined by the nucleotide sequences and the encoding of the protein by the gene.
The secondary structure is the regular folding in regions of the polypeptide chain and the most common are the alpha helix and beta pleated sheets.
In the video the alpha helices are then described as being an arrangement of the amino acids in the regular helical formation. There is hydrogen bonding between the oxygen in the peptide bonds and the hydrogen of every 4th amino acid where the hydrogen bonds running nearly parallel to the axis of the helix (C=O —-NH2). There are 3.6 amino acid residues for every turn in the helix and their R groups face the outside and perpendicular of the cylindrical helix axis.
In the video Mr. BiochemJM describes the Alpha helix in considerable depth. He describes it as wrapping around an imaginary central rod in a coiling configuration.
The alpha helix is the most common form of coiling and forms more readily because of the optimal use of internal hydrogen bonding. All the peptide bonds in the helix are involved in hydrogen bonding except the ones at the ends. Each successive turn in the helix is held together by 3 or 4 hydrogen bonds which gives the helix collective stability.
In the helix some amino acids are considered undesirable because they can weaken the structure. One of these is proline which has that ring structure that has bonding with the alpha amine group (NH3) so there is one less hydrogen available for bonding. It produces a destabilizing ‘kink’ in the helix. Thus it is usually found at the ends of the alpha helix and it can sometimes terminate the helix by causing alterations in the direction of the polypeptide chain.
According to Mr. JM, “We can lebel proline as a bad boy.”
Glycine can also compromise the structure of the alpha helix. Its R group is the smallest atom being hydrogen so it has high conformational flexibility.
Amino acid residues with charges can also stabilize or destabilize the helix. Like charges repel each other which may cause ‘kinks’ in the helical structure. Large R groups can cause steric interference which will stop the formation of the helix. The amino acids with the large R groups cannot bond closely to give proper turns in the structure. The turn in the helix can facilitate the critical interactions of the amino acid side chains. The positive and negative side chains are usually located 3 – 4 residues away so an ion pair can form when there is the twist. Two aromatic amino acid residues similarly spaced from each other can lead to hydrophobic interactions which will in turn stabilize the helix.
Electric dipoles are also formed at the ends of the helix. This is due to hydrogen bonding. The negatively charged end is on the amino terminal as not the amino acid residues do not bond fully by hydrogen bonding. The positively charged end is the carboxyl end where the negative end of the helix is stabilized.
Image from http://ars.els-cdn.com/content/image/1-s2.0-S0005273612003860-gr1.jpg
The video then goes on to describe the second structure of beta pleated sheets.
In the beta pleated sheets the hydrogen bonds from between the peptide bonds on the same or different polypeptide chains. The planarity of the peptide bonds forces the polypeptide to be pleated with side chains of the amino acids protruding from above and below the sheet. The sheets can be parallel or anti parallel which depends on the C and N terminal end orientation. It is parallel when the terminals are the same on one end and in anti parallel sheets the Terminal ends alternate.
The tertiary structure refers to the spatial arrangement of amino acids that are far apart in the linear sequence as well as those residues that are adjacent. The main driving force for the tertiary structure in a globular protein is the hydrophobic effect where the hydrophobic groups and hydrophilic groups react differently and fold according to the medium to which they are exposed. eg, when exposed to water the hydrophobic groups will fold towards the interior of the structure while the hydrophilic groups are on the surface. This is the hydrophobic effect. Once folded the 3D structure is also maintained by electrostatic forces, hydrogen bonding and if present the covalent disulphide bonds.
The strengths of these bonds are also described. The disulphide bonds are the least frequent and don’t really contribute to the maintenance of the structure. The hydrophobic interactions are weak but collectively they are really strong.
Image obtained from :http://www.dynamicscience.com.au/tester/solutions/chemistry/foodchemistry/proteinstrct.gif
The ionic bond is also called the salt bridge. The tertiary structure is based on interactions of the R groups of the amino acid residues.
Mr. JM then moves on to describe in detail the main details of each type of bond which was in depth and properly explained. This explanation was useful because it linked the bonds to the turns in the secondary structure which gave the importance of the turns in the alpha Helix.
The hydrophobic forces are important in determining protein structure, folding and stability. They try to minimize contact with water. It increases entropy which makes it energetically favored. All the other bonds are also important.
The video then goes on to describe the effects of changes in the sequence of the chain as in sickle cell anemia where glutamate is replaced by valine in the structure of hemoglobin.
Image obtained from :http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/Gifs/HBBmutseq_2.gif
A question was asked on the importance of this substitution with respect to the amino acids themselves. It provided crucial information into why the substitution can be problematic.
Finally the video deals with the Quaternary structures which deals with at least 2 polypeptide chains. These structures provide more stability. They also participate in substrate channeling. This occurs in Oligomers because they are basically structures with more than one polypeptide chain.
Proteins can become denatured. Their natural or native structures may be altered and their biological activity changed or destroyed but the primary structure is not affected. Denaturing refers to the loss of folding dealing with the primary or secondary structure. Based on the conditions some proteins can return to their native form but under extreme conditions like excessive heating the process is irreversible.
Several factors can denature proteins like:
This information was obtained directly from the video.
In heat denaturation the main bonds being broken are the hydrogen bonds. It is a cooperative process because the destabilizing of some parts will reduce the stability of other parts. This is shown by the abrupt change in enzyme activity over a slow increase in temperature .The structure can change for example in frying eggs the albumins unfold and coagulate which drastically reduces the solubility of the proteins.
Enzymes lose all catalytic activity when denatured. The video then goes on to describe the different types of denaturation and their applications in a lab setting like chemical denaturation.
The Anfinsen Experiment is also described.
From the size of this blog post alone there was only one problem with the video and it was its sheer length and volume of information provided. It cannot be watched in one straight sitting. It could be divided where basics and alpha helix are 1 video and the remainder in the other Otherwise the video was very informative from a level 1 perspective and it it covers all the bases. Thanks for another wonderful video Mr. BiochemJM!
Next I will briefly cover Enzymes! As always thanks for reading! 🙂
So many Topics so little time!!!!!!