Macromolecular Interactions and Molecular Machineries in Biological Systems

Kostas Tokatlidis

School of Biological Sciences, University of Manchester, UK

All living organisms obey chemical and physical laws. The chemistry of life is mainly organic, takes place mainly in aqueous solution, in a narrow temperature range and it is vastly complex. All chemical reactions in living organisms are coordinated by polymeric molecules (nucleic acids, lipids and proteins), whose unique chemical and physical properties ensure the organisation, growth and reproduction. Whilst nucleic acids are the central genetic information stores in all cells, the building architecture and function of individual cells, tissues and organisms relies on proteins. For many of these proteins, their specific point of action is distant from the site of their biosynthesis. It is therefore essential for the cell to have accurate mechanisms for correct protein targeting. This protein targeting problem has been recognised as a central problem of modern biology in the last 20 years and indeed specific targeting mechanisms for the various subcellular compartments have been identified. These operate by specialised macromolecular protein machineries dedicated to recognise and transport proteins. The magnitude of these targeting events is reflected by the fact that almost one half of the cell’s proteins are translocated across or inserted into a membrane. Energy for this and other processes in the cells (motion, active transport of molecules and biosynthesis of large macromolecules from simpler molecules) is provided by one basic chemical fuel, a small molecule called ATP. This universal energy carrier (the gasoline, so to speak, for the cell) is produced in special compartments within the cell called mitochondria. Without mitochondria, a great number of organisms including man, animals, fungi and plants would be unable to use oxygen to extract energy from the fooodstuffs that nourish them. Mitochondria are made up of about a thousand different proteins. Strikingly, almost all of them are synthesised outside mitochondria and then imported into mitochondria. The import process is hence crucial for the proper function of the cell, and many human diseases are related to a malfunction of the mitochondrial import system. We are studying the orchestration and coordination of the protein import process in mitochondria by specialised macromolecular assemblies and how the chemical and physical properties of these polymeric complexes ensure proper biological function.