Aims

• To illustrate the importance of macromolecular structures in understanding the molecular basis of biological function.
• To introduce the concept of structural domains.
• To describe how domains can be assigned automatically.

Objectives

After this lecture you will:

• be aware that knowing the three-dimensional structures of macromolecules can give new insights into biological function, enabling scientists to formulate new hypotheses and design new experiments;
• know that proteins often consist of structural domains;
• know how to interpret contact maps;
• understand, in outline, how domain assignment can be performed.

Supplementary Material

The structure of a bZIP transcription factor bound to DNA (PDB entry 1GD2) is described in:

Fujii, Y., Shimizu, T., Toda, T., Yanagida, M. and Hakoshima, T. (2000) Structural basis for the diversity of DNA recognition by bZIP transcription factors. Nature Structural Biology, 7, 889-893. (Pubmed)

The structures of elongation factors involved in nucleotide exchange (including PDB entry 1G7C) are described in:

Andersen, G.R., Valente, L., Pedersen, L., Kinzy, T.G. and Nyborg, J. (2001) Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Balpha complex. Nature Structural Biology, 8, 531-534. (Pubmed)

The structural basis for the biological function of elongation factors is described in a review article:

Andersen, G.R., Nissen, P. and Nyborg, J. (2003) Elongation factors in protein biosynthesis. Trends in Biochemical Sciences, 28, 434-441. (Pubmed)

Roderick MacKinnon was awarded the Nobel Prize in Chemistry 2003 "for structural and mechanistic studies of ion channels".

The structure of the potassium channel protein from Streptomyces lividans (PDB entry 1BL8) is described in:

Doyle, D.A., Morais Cabral, J., Pfuetzner, R.A., Kuo, A., Gulbis, J.M., Cohen, S.L., Chait, B.T. and MacKinnon, R. (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science, 280, 69-77. (Pubmed)

The value of atomic structures in understanding the function of potassium channels is discussed in a review article:

MacKinnon, R. (2003) Potassium channels. FEBS Letters, 555, 62-65. (Pubmed)

Several contact maps are shown on The Protein Kinase Resource web site.

The algorithm used by DOMAK to identify structural domains is described in:

Siddiqui, A.S. and Barton G.J. (1995) Continuous and discontinuous domains: an algorithm for the automatic generation of reliable protein domain definitions. Protein Science, 4, 872-884. (Pubmed)

The algorithm used by STRUDL to identify structural domains is described in:

Wernisch, L., Hunting, M. and Wodak, S.J. (1999) Identification of structural domains in proteins by a graph heuristic. Proteins: Structure, Function and Genetics, 35, 338-352. (Pubmed)