Protein folding

Wednesday 29 June 2011

 

This article by Mike Williams-Rice is a nice read for HL students to link with the folding of polypeptides to produce the tertiary structure of proteins.  It is great to associate the syllabus points with actual research results.

There are four levels of protein structure.  See Protein HL

The sequence and number of amino acids in a polypeptide determines the primary structure.  Of course this sequence is directly coded by the DNA nucleotide sequence of the gene.  Amino acids are bonded together by the peptide bond, a strong covalent bond created by the condensation reaction between two amino acids. The number of possible combinations indicates the vast variety of proteins that can exist.  For example, a polypeptide of 600 amino acids, coded by a gene of at least 200 nucleotides, can exist in 20600 different permuations!  Naturally, not all of these are viable but the number is so large and this is for only the 600 amino acid chains and proteins can be made of any number of amino acids! 

The secondary structure is due to the hydrogen bonding interactions between the -OH and HN- groups of amino acids that are 4 amino acids apart.  These bonds create the alpha helix coiling or the beta pleated sheets.  The variable R side chain does not affect this structure.

The tertiary structure is directly due to the variable R side chain of each amino acid in the polypeptide.  Some R groups are polar, others are nonpolar, some are acidic while others are basic.   These differences cause the chain to fold so the nonpolar R groups are tucked away inside the protein to avoid contacting the watery environment, such as integral membrane proteins that are embedded within the nonpolar plasma membrane.  The interactions between the R groups include hydrogen bonding, ionic bonds, disulfide bridges, hydrophobic interactions.  Williams-Rice describes how calcium ions are implicated in the folding process of an enzyme implicated in a lipid metabolism in lysosomes.

"Impairment of calcium homeostasis further compromises the folding of already destabilized, mutated versions of the enzyme glucocerebrosidase (GC). Slowing the folding process ever so slightly by regulating calcium stabilizes GC and lets it fold properly and enter the lysosome, where it breaks down lipids."[1]

Finally, the quaternary structure arises from the interactions of two or more polypeptdies. Again the same kind interactions hold the polypeptide chains together.


Footnotes

  • 1. Williams-Rice, Mike. "Futurity.org – Possible rescue for misfolded proteins." Futurity.org . N.p., n.d. Web. 29 June 2011. .

Tags: tertiary amino acid mutation