PROTEIN STRUCTURE

Proteins | Protein Structure | Protein Folding | Movies

An analysis of known protein structures is necessary for an understanding of protein folding and stability.

Protein structure is broken down into four levels:

Primary structure refers to the "linear" sequence of amino acids.

Proteins are large polypeptides of defined amino acid sequence. The sequence of amino acids in each protein is determined by the gene that encodes it. The gene is transcribed into a messenger RNA (mRNA) and the mRNA is translated into a protein by the ribosome.

Graphics courtesy of National Human Genome Research Institute (NHGRI) http://www.nhgri.nih.gov/DIR/VIP/
by artist Darryl Leja

Primary structure is sometimes called the "covalent structure" of proteins because, with the exception of disulfide bonds (see below), all of the covalent bonding within proteins defines the primary structure. In contrast, the higher orders of proteins structure (i.e. secondary, tertiary and quartenary) involve mainly noncovalent interactions.

Secondary structure is "local" ordered structure brought about via hydrogen bonding mainly within the peptide backbone.

The most common secondary structure elements in proteins are the alpha (a) helix and the beta (b) sheet (sometime called b pleated sheet).

Here is a visualization of alpha helix: ball and stick, backbone and the secondary structure cartoon (linguini diagram).

Pictures courtesy of Bernhard Rupp (br@llnl.gov)

Here we see the hydrogen bond network in a 2-stranded, antiparallel Beta-sheet. The side chains are sticking out above or below the plane of the picture. It less clear cut than in the case of the helix, in which direction to initially trace a beta sheet strand. The beta sheet can be infinitely extended due to the repeatable H-bonding pattern to either side of a strand.

Pictures courtesy of Bernhard Rupp (br@llnl.gov)

Tertiary structure is the "global" folding of a single polypeptide chain.

A major driving force in determining the tertiary structure of globular proteins is the hydrophobic effect. The polypeptide chain folds such that the side chains of the nonpolar amino acids are "hidden" within the structure and the side chains of the polar residues are exposed on the outer surface. See 3D visualization of Lysozyme.

Lysozyme

Hydrogen bonding involving groups from both the peptide backbone and the side chains are important in stabilizing tertiary structure.

The tertiary structure of some proteins is stabilized by disulfide bonds between cysteine residues.

Quartenary structure involves the association of two or more polypeptide chains into a multi-subunit structure.

Quartenary structure is the stable association of multiple polypeptide chains resulting in an active unit. Not all proteins exhibit quartenary structure. Usually, each polypeptide within a multisubunit protein folds more-or-less independently into a stable tertiary structure and the folded subunits then associate with each other to form the final structure.

Quartenary structures are stabilized mainly by noncovalent interactions; all types of noncovalent interactions: hydrogen bonding, van der Walls interactions and ionic bonding, are involved in the interactions between subunits. In rare instances, disulfide bonds between cysteine residues in different polypeptide chains are involved in stabilizing quartenary structure.

Movies of computer simulations of protein folding

Author: Tug Sezen