Biophysical Methods:

A Tour of Protein Structure

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The structure of myoglobin; the ribbon represents the path of the polypeptide chain and is color coded blue at the N-terminus, running through to red at the C-terminus. Note the organization into many helical segments.


The structures of proteins are much more complex than simple organic chemicals, because the size of the molecules allow for many possible 3-D arrangements of the same covalent bonded structure.

Protein structure may be interpreted in terms of a hierarchy:

Primary structure is the sequence of amino acids in the polypeptide chain. This represents the covalent bonding in the protein molecule.
e.g. Val-Leu-Ser-Glu-Gly-Glu-Trp-Gln-Leu-Val- represents the first ten amino acids of myoglobin (out of 153 total).

Secondary structure is the organization of the polypeptide into regular repetitive patterns over short segments of 5-15 amino acids, for example the helical segments in the myoglobin structure.

Tertiary structure is the overall folding of the whole polypeptide.

Quaternary structure is the grouping of several protein molecules into a single larger entity; the subunits may act cooperatively with each other to give the grouping special properties not possessed by the single subunit. Not all proteins have a quarternary structure, e.g. a single myoglobin molecule functions by itself, but its close relative, hemoglobin, is a tetramer of four globin subunits. Each globin is structurally very similar to myoglobin.

The size of proteins precludes dealing with entire protein molecules on an atom-by-atom basis. If we start by understanding the structures of the amino acids, we can deal with proteins as chains of amino acids, and hide the atom-by-atom detail when looking at the whole structure. Eliminating the detail and using schematic representations allows the higher orders of structure to be seen more clearly.

When necessary, we may look at atom by atom details of small regions of an entire protein. This is greatly assisted by the availability of computer software which allows selective display of portions of macromolecular structures. Structural data for display is maintained by the Protein Data Bank at Brookhaven National Laboratory, and is accessible on the World Wide Web.


How secondary structure determines folding

Common folding patterns of protein tertiary structure

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