Tertiary Structure
Protein tertiary structure is due to interactions between R groups in the protein. Note that these R groups MUST be facing each other to interact. There are four types of tertiary interactions: hydrophobic interactions, hydrogen bonds, salt bridges, and sulfur-sulfur covalent bonds. Each of these will be explored below.
Hydrophobic interactions are due to non-polar sidechains "liking" to be near each other and away from any polar or charged sidechains. Hydrophobic interactions occur when two non-polar sidechains interact. These interactions are often found on the inside of the protein since the cellular environment is mostly aqueous.
Hydrophobic Interactions Triose phosphate isomerase (TPI) is an enzyme involved in glycolysis. Hydrophobic sidechains flash yellow, then cpk colors. Note the interaction between sidechains with backbone highlighted in yellow at the end of the sequence. (2YPI.pdb)
Are hydrophobic residues located mostly on the surface of the protein or on the inside of the protein? Why do you think that is the case?
Hydrogen bonds form between polar groups – one of which MUST have a polar hydrogen atom. Hydrogen atoms are polar when bonded to either an N or O atom. That hydrogen is then attracted to another N or O.
Hydrogen Bonding Between Polar Groups Look at these two sidechains in GATA-1/FOG-1 (1Y0J.pdb). See if you can determine which two atoms will form a hydrogen bond.
Do one or both of the groups have a polar hydrogen?
Salt bridges are due to the attractions of positively charged sidechains to negatively charged sidechains. Click on the buttons below to view the positively and negatively charged sidechains in TPI. (2YPI.pdb)
Positively Charged Sidechains Positive sidechains flash blue in this image.
Negatively Charged Sidechains Negative sidechains flash red in this image.
Charged Interactions Note the interaction between the two oppositely charged sidechains with the purple backbone.
Do these interactions occur on the inside or outside of the protein? Why?
Covalent sulfur-sulfur (disulfide) bonds only form between two cysteine amino acid residues (an amino acid that is part of the peptide chain). The cysteines lose the hydrogen from the -SH group and form an S-S bond.
Disulfide Bonds Of the three S-S bonds in insulin, this S-S bond, shown here, is between two cysteines on the same chain (2HIU.pdb).
How does the strength of this interaction compare to the other three interactions?
Tertiary structure refers to the interactions between amino acid sidechains within a protein. These interactions will only occur if the sidechains are near each other in three-dimensional space; the interactions between sidechains often drive protein folding.