Tertiary structure refers to the three-dimensional structure of the entire polypeptide chain.
Tertiary structure is important!
The function of a protein (except as food) depends on its tertiary structure. If this is disrupted, the protein is said to be denatured [Discussion], and it loses its activity.
A mutation in the gene encoding a protein is a frequent cause of altered tertiary structure.
- denatured enzymes lose their catalytic power
- denatured antibodies can no longer bind antigen
- The mutant versions of proteins may fail to reach their proper destination in the cell and/or be degraded.
- Cystic fibrosis is caused failure of the mutant CFTR protein to reach its destination in the plasma membrane [More].
- Diabetes insipidus is caused by improper folding of mutant versions of
- Familial hypercholesterolemia is caused by failure of mutant low-density lipoprotein (LDL) receptors to reach the plasma membrane. [Discussion]
- Osteogenesis imperfecta is caused by failure of mutant Type I collagen molecules to assemble correctly. [More]
- Mutant proteins may aggregate forming insoluble, nonfunctional deposits. This is particularly likely if the mutation causes hydrophobic R groups to be displayed at the surface of the molecule rather than in its interior.
- Alzheimer's disease is characterized by insoluble protein deposits - called amyloid - in the brain.
- Bovine spongiform encephalopathy (BSE) ("mad cow") disease and the human version - Creutzfeldt-Jakob disease (CJD) - are characterized by amyloid deposits in the brain of a mutant version of the prion protein.
The normal protein has lots of alpha helical regions and is soluble. In the mutant version, the alpha helix is converted into beta conformation and the protein becomes insoluble.
Curiously, tiny amounts of the mutant version can trigger the alpha-to-beta conversion in the normal protein. Thus the mutant version can be infectious. There have been several cases in Europe of people ill with Creutzfeldt-Jakob disease that may have acquired it from ingesting tiny amounts of the mutant protein in their beef.
The images (courtesy of Dr. D. R. Davies) represent the tertiary structure of the antigen-binding portion of an antibody molecule. Each circle represents an alpha carbon in one of the two polypeptide chains that make up this protein. (The filled circles at the top are amino acids that bind to the antigen.) Most of the secondary structure of this protein consists of beta conformation, which is particularly easy to see on the right side of the image.
Do try to fuse these two images into a stereoscopic (3D) view. I find that it works best when my eyes are about 18" from the screen and I try to relax so that my eyes are directed at a point behind the screen.
Where the entire protein or parts of a protein are exposed to water (e.g., in blood or the cytosol), hydrophilic R groups are found at the surface; hydrophobic R groups are buried in the interior.
14 July 2000