Proteins

Introduction to Protein Structure

Proteins

Proteins are not linear molecules as suggested when we write out a "string" of amino acid sequence, -Lys-Ala-Pro-Met-Gly- etc., for example. Rather, this "string" folds into an intricate three-dimensional structure that is unique to each protein. It is this three-dimensional structure that allows proteins to function. Thus in order to understand the details of protein function, one must understand protein structure.

In order to fully explore protein structure in detail we will use a number of different types of molecular models, including backbone only, ribbon diagrams and "cartoon" views.

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.

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).

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

A major driving force in dertemining 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.

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

The teriary 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 stablized mainly by noncovalent interactions; all types of noncolvalent 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.