Proteins Structure and Function

Overview of book chapters:

This book will address the structure and function of proteins in 12 subsequent chapters each with a definitive theme. After an initial chapter describing why one would wish to study proteins and a brief historical background the second chapter deals with the ‘building blocks’ of proteins, namely the amino acids together with their respective chemical and physical properties. No attempt is made at any point to describe the metabolism connected with these amino acids and the reader should consult general textbooks for descriptions of the synthesis and degradation of amino acids. Chapter 3 covers the assembly of amino acids into polypeptide chains and levels of organizational structure found within proteins. Almost all detailed knowledge of protein structure and function has arisen through studies of globular proteins but the presence of fibrous proteins with different structures and functional properties necessitated a separate chapter devoted to this area (Chapter 4). Within this class the best understood structures are those belonging to the collagen class of proteins, the keratins and the extended ? sheet structures such as silk fibroin. The division between globular proteins and fibrous proteins was made at a time when the only properties one could compare readily were a protein’s amino acid composition and hydrodynamic radius. It is now apparent that other proteins exist with properties intermediate between globular and fibrous proteins that do not lend themselves to simple classification. However, the ‘old’ schemes of identification retain their value and serve to emphasize differences in proteins.

Membrane proteins represent a third group with different composition and properties. Most of these proteins are poorly understood, but there have been spectacular successes from the initial low-resolution structure of bacteriorhodopsin to the highly defined structure of bacterial photosynthetic reaction centres. These advances paved the way towards structural studies of G proteins and G-protein coupled receptors, the respiratory complexes from aerobic bacteria and the structure of ATP synthetases.

Chapter 6 focuses both on experimental and computational methods of comparing proteins where in silico methods have become increasingly important as a vital tool to assist with modern protein biochemistry. Chapter 7 focuses on enzymes and by discussing basic reaction rate theories and kinetics the chapter leads to a discussion of enzyme-catalysed reactions. Enzymes catalyse reactions through a variety of mechanisms including acid–base catalysis, nucleophilic driven chemistry and transition state stabilization. These and other mechanisms are described along with the principles of regulation, active site chemistry and binding.

The involvement of proteins in the cell cycle, transcription, translation, sorting and degradation of proteins is described in Chapter 8. In 50 years we have progressed from elucidating the structure of DNA to uncovering how this information is converted into proteins. The chapter is based around the structure of two macromolecular systems: the ribosome devoted towards accurate and efficient synthesis and the proteasome designed to catalyse specific proteolysis. Chapter 9 deals with the methods of protein purification. Very often, biochemistry textbooks describe techniques without placing the technique in the correct context. As a result, in Chapter 9 author have attempted to describe equipment as well as techniques so that students may obtain a proper impression of this area.

Structural methods determine the topology or fold of proteins. With an elucidation of structure at atomic levels of resolution comes an understanding of biological function. Chapter 10 addresses this area by describing different techniques. X-ray crystallography remains at the forefront of research with new variations of the basic principle allowing faster determination of structure at improved resolution. NMR methods yield structures of comparable resolution to crystallography for small soluble proteins. In ideal situations these methods provide complete structural determination of all heavy atoms but they are complemented by other spectroscopic methods such as absorbance and fluorescence methods, mass spectrometry and infrared spectroscopy. These techniques provide important ancillary information on tertiary structure such as the helical content of the protein, the proportion and environment of aromatic residues within a protein as well as secondary structure content.

Chapter 11 describes protein folding and stability – a subject that has generated intense research interest with the recognition that disease states arise from aberrant folding or stability. The mechanism of protein folding is illustrated by in vitro and in vivo studies. Whilst the broad concepts underlying protein folding were deduced from studies of ‘model’ proteins such as ribonuclease, analysis of cell folding pathways has highlighted specialised proteins, chaperones, with a critical function to the overall process. The GroES–GroEL complex is discussed to highlight the integrated process of synthesis and folding in vivo.

The final chapter builds on the preceding 11 chapters using a restricted set of well-studied proteins (case studies) with significant impact on molecular medicine. These proteins include haemoglobin, viral proteins, p53, prions and ?1-antitrypsin. Although still a young subject area this branch of protein science will expand in the next few years and will rely on the techniques, knowledge and principles elucidated in Chapters 1–11. The examples emphasize the impact of protein science and molecular medicine on the quality of human life.

Addition material

Protein Visualization Sources

Further Reading links

Proteing Database Files