Protein structure

Protein structure

8/1/03. By Richard Twyman

The three-dimensional structure of a protein is crucial to its function.

Genes encode proteins by providing a sequence of nucleotides that is translated into a sequence of amino acids. The sequence of amino acids is known as the primary structure of the protein. However, in order to function correctly, this amino acid chain must fold up into a complex three-dimensional shape.

Protein folding involves the formation of local structural motifs such as helices and sheets (secondary structures) and the coalescence of these individual structures into an overall three-dimensional configuration (tertiary structure). The greatest achievement of the human genome is its ability to encode the precise three-dimensional shapes of thousands of proteins using linear sequences. It is a trick we still do not fully understand.

Protein structure is essential for correct function because it allows molecular recognition. For example, enzymes are proteins that catalyse biochemical reactions. The function of an enzyme relies on the structure of its active site, a cavity in the protein with a shape and size that enable it to fit the intended substrate very snugly. It also has the correct chemical properties to bind the substrate efficiently. The active site also contains certain amino acids that are involved in the chemical reaction catalysed by the enzyme.

Not all proteins are enzymes, but all in some way rely on molecular recognition in order to perform their functions. Transport proteins such as haemoglobin must recognise the molecules they carry (in this case oxygen), receptors on the cell surface must recognise particular signalling molecules, transcription factors must recognise particular DNA sequences (see Gene expression ) and antibodies must recognise specific antigens. The functional integrity of the cell depends critically on protein-protein interactions, particularly on the formation of multi-protein complexes.

Mutations that cause human diseases often disrupt protein structure and therefore abolish normal function. This occurs if one amino acid is replaced with another that has completely different chemical properties or if the sequence of amino acids in a protein is truncated or radically changed. Such changes alter the way the protein folds and prevent the recognition of interacting molecules.

Polymorphisms in the coding sequence of a gene can also affect protein structure but do so in more subtle ways, e.g. by replacing one amino acid with another that has similar chemical properties. This is how single-nucleotide polymorphisms influence drug response patterns. For example, they may cause subtle alterations to the structure of the receptors with which drugs interact, or subtle changes to the activity of enzymes responsible for drug metabolism.

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