BIOCHEMISTRY - L. Stryer - 1984

VOLUME 1

PART I. CONFORMATION AND DYNAMICS

CHAPTER 2. BASIC CONCEPTS OF PROTEIN STRUCTURE AND FUNCTION

Summary

Proteins play a pivotal role in virtually all biological processes. All Enzymes—catalysts of Chemical Reactions in biological systems—are proteins. Consequently, proteins dictate the course of biological transformations within Cells. Proteins are also involved in a multitude of other Functions, such as TRANSPORT AND STORAGE, coordinated movement, mechanical support, immunological defense, excitability, growth regulation, and differentiation.

The fundamental structural unit of proteins is The amino acid. All proteins in every living Organism, from Bacteria to humans, share the exact same set of twenty Amino Acids. Amino acid side chains vary in size, shape, charge, hydrogen-bonding capacity, and chemical reactivity. They can be classified into the following groups: a) aliphatic side chains—Glycine, Alanine, valine, leucine, isoleucine, and Proline; b) hydroxylated aliphatic side chains—Serine and Threonine; c) aromatic side chains—phenylalanine, Tyrosine, and Tryptophan; d) basic side chains—Lysine, Arginine, and Histidine; e) acidic side chains—aspartic acid and glutamic acid; f) amide side chains—asparagine and glutamine; g) sulfur-containing side chains—Cysteine and Methionine.

Amino acids, typically numbering at least one hundred, are linked together by peptide bonds to form a polypeptide chain. The peptide bond connects the ос!!!-carboxyl group of one amino acid with the a-amino group of another. In certain proteins, individual side chains are linked by disulfide bridges formed through The oxidation of cysteine residues. Proteins consist of one or more polypeptide chains. Each protein features a unique Amino Acid Sequence that is genetically determined. The amino acid sequence of proteins is determined as follows. First, the overall Amino Acid Composition is established by subjecting an acid hydrolysate of the protein to Ion-exchange Chromatography, and the N-terminal amino acid residue is identified using an N-terminal-specific reagent, such as dansyl chloride. The next step involves the Specific Cleavage of the protein into smaller Peptides. This is commonly achieved using Trypsin, which hydrolyzes proteins at peptide bonds formed by the carboxyl groups of lysine and arginine residues. The Amino acid sequences of the resulting peptides are then determined by the Edman Degradation method, which involves the sequential removal of the N-terminal residue. Finally, the arrangement of peptides within the protein is established by aligning the amino acid sequences of overlapping peptides.

The decisive factor determining the biological function of proteins is their conformation, i.e., the spatial arrangement of the atoms in the protein molecule. Three regularly repeating polypeptide chain Conformations are known: the α-Helix, pleated α-sheets, and the Collagen helix. Short segments of the α-helix and β-sheets are found in many proteins. Crucially, the three-dimensional Structure of a protein is dictated entirely by its amino acid sequence; this was first discovered during studies on Ribonuclease. It was demonstrated that a reduced, unfolded ribonuclease molecule is capable of spontaneously refolding into its native structure (forming the correct combination of disulfide bridges between cysteine residues) and fully regaining its enzymatic activity once mercaptoethanol and urea are removed and the denatured enzyme is exposed to atmospheric oxygen. Protein folding proceeds via the association of short polypeptide segments that form transient α-helical or β-sheet conformations.