2 - Physiological Structure and Function of Proteins

Abstract

This chapter discusses the physiological structure and function of proteins. It is mentioned that the three-dimensional structures of proteins are dictated by their linear sequences of amino acids. Molecular structure of proteins and techniques for the determination of the structures of proteins, bulk properties of proteins, and relationship of protein structure to function, are discussed in detail. Proteins are structured in such a way that their polar amino acids tend to be directed towards the aqueous solvent while the nonpolar or hydrophobic residues tend to point towards the interior of the protein. The three-dimensional structures of proteins can be determined by a variety of techniques, including circular dichroism (for regular structure), x-ray crystallography, two-dimensional NMR, and theoretical techniques. The three-dimensional structures of proteins determine bulk properties of these proteins, such as their behavior towards titration with acids or bases, their isoionic points, and their migration in electric fields, as in electrophoresis. The relationships of the conformations of proteins to their functions concentrate on one aspect of fundamental importance to cell physiology, membrane polypeptides, and proteins. The use of the methods of conformational analysis based on the principles of protein structure described in the chapter has resulted in being able to identify critical residues of an oncogenic protein that are vital to their function, to design peptides that selectively inhibit oncogenic “ras-p21,” and to detect differences in signal transduction pathways induced by oncogenic and normal p21 protein. Under function of ras-p21, it is mentioned that when activated by ras or other intracellular proteins, raf binds to and phosphorylates an extracellular mitogen-stimulated kinase called MEK, which in turn, binds to and phosphorylates a vital protein, MAP kinase (mitogen-activated protein kinase). Acid-base properties of amino acids, protein charge and solubility, titration of proteins, protein charge and electrophoresis are discussed in detail under properties of proteins and proteins as polyelectrolytes.