All I know about .. protein

on Wednesday, October 19, 2011
can be summarized in a little post here.

Protein and Its Structure
A protein is a polymer of amino acids which are joined together by the peptide bonds. Protein encoded by the genetic code has a polypeptide backbone that is usually between 50 to 2000 amino acids long and up to 20 different kinds of side chains. The flat sequence of the amino acids in a protein form its primary structure. The two common folding patterns in proteins are alpha-helix and beta-sheet, which form the secondary structure of a protein. Tertiary and quaternary structures are determined by the three-dimensional shape of the particular protein and its interactions with other large proteins in its surrounding.

The particular conformation of a protein is determined by its composition. The conformation is generally stable if it minimizes the free energy of the protein. The following table lists all the 20 different amino acids which are coded by the :

Amino Acid NameAbbreviationsAmino Acid NameAbbreviations
Aspartic AcidAsp, DArginineArg, R
AsparagineAsn, NAlanineArg, R
CysteineCys, CGlutamic AcidGlu, E
GlutamineGln, QGlycineGly, G
HistidineHis, HIsoleucineIle, I
LeucineLeu, LLysineLys, K
MethionineMet, MPhenylalaninePhe, F
ProlinePro, PSerineSer, S
TheonineThr, TTrytophanTrp, W
TyrosineTyr, YValineVal, V
Table 1. The twenty amino acids encoded by the DNA (Alberts, et al., 2008)

A protein domain is typically a smaller stable structure formed out of 40 to 350 amino acids, roughly, and can be found in many different proteins through the process known as domain shuffling. In particular, combinations of two domains are common and they can occur in roughly twenty five percents of all known proteins across all living beings. Just like in DNA, due to evolutionary preservations, similarities in protein sequences may suggest relatedness in functions. Proteins may come in different sizes, such as long helical filaments, fibre-like strings or even mashes of unstructured polypeptides.

Image 1. A protein with 3 domains (

Protein Binding
A protein can bind to another molecule, generally called a ligand, at its binding site through weak non-covalent bonds such as the hydrogen bond, the electrostatic bonds and the van der Waals forces. According to Alberts, et al. (2008, p. 153),
"Because each individual bond is weak, effective binding occurs only when many of these bonds form simultaneously. Such binding is only possible only if the surface contours of the ligand molecule fit very closely to the protein, matching it like a hand in a glove"
Image 2. Binding of a ligand to the binding site (Alberts, 2008)

The binding of a ligant to a protein causes a conformational change, which is reversible. Allosteric enzymes have two or more binding sites, each of which can be either a binding site or a regulatory site. As mentioned before, the interactions between these sites cause a conformational change of the structure of the protein. Two ligands are called 'coupled' if the presence of one of them in a binding site induces a conformational change that encourages the binding of the other ligand as well. Similarly, a particular ligand may also competitively induce a conformational change that discourages the binding of the other ligand. We can then view allosteric proteins as switches that regulate the interactions of intercellular molecules. Metabolic pathways in a cell are controlled by such feedback regulations.

For a good case study, see the aspartate transcarbamylase enzyme from E. coli. Also take a look at this video of the purine metabolic pathway.

Enzymes is a class of protein that binds its substrates and catalyzes chemical reactions by selectively stabilizing transition states. Enzymes can use simultaneous acid and base catalysis by having the appropriate positions of surface molecules. Catalysis can be done by either holding the substrates together in an alignment that encourages reaction between them, stabilizing the charges of the reaction intermediates or straining the bonds in the substrate to encourage reactions. Multienzymes structures are particularly helpful in helping to regulate and increase cellular metabolism, and in turn, the catalytic activities of enzymes are regulated by the cell through either negative (feedback inhibition) or positive regulations.

Post-translational modifications
Proteins are subjected to many post-translational modifications. Another way to regulate protein functions is a cell is through protein phosphorylation, which is the addition of a phosphate group to the amino acid side chains. This causes conformational changes in the protein and allows the possibility of new binding between one protein to other different proteins. Phosphorylation is catalyzed by protein kinase enzyme, while in reverse, dephosphorylation is catalyzed by the protein phosphatase enzyme. For example of protein kinases, see the cyclin-dependent protein kinase (Cdk) which phosporylates series and theonines, and Src protein, which is a kinase for tyrosine.

Another way for regulations through phosphate groups occur in eukaryotic cells through the binding and hydrolysis of GTP into GDP in the protein. GTP-binding proteins (GTPases) is the class of proteins that contain the variations of the GTP-binding domains. One example of this is the Ras protein.

Other protein functions
Movements in cells can be accomplished through motor proteins, which are capable of unidirectional conformational changes that produce movements. This is used, for instance, to move chromosomes around the cell during mitosis or to move organelles within the cells. Finally, we have the membrane-bound pump proteins that allow the removal of hydrophobic molecules through the cytoplasm. (A lecture on motor protein can be found here).

Complex Interactions
Large protein machines can be formed through the combinations of many protein molecules. Protein machines are activated when needed at a specific location in the cell. One protein in a cell usually interact with at least 5 other different proteins. This is in addition to the numerous feedback loops and inhibitions that occur in an interaction. Proteomics is a particular field of study that attempt to understand the interactions between complex intracellular protein networks.

Alberts, B., et al. (2008). Molecular Biology of the Cell (5th ed). Garland Science: New York.


Chloe said...

The fusion protein was purified several times by affinity binding to an amylose resin. Protein function is varied based on different chemicals.

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