Proteins, polypeptide chain folding

Several motifs usually combine to form compact globular structures, which are called domains. In this book we will use the term tertiary structure as a common term both for the way motifs are arranged into domain structures and for the way a single polypeptide chain folds into one or several domains. In all cases examined so far it has been found that if there is significant amino acid sequence homology in two domains in different proteins, these domains have similar tertiary structures. 

The sequence of amino acid units in a protein is always specified by a gene. The sequence determines how the polypeptide chain folds and how the folded protein functions. For this reason much effort has gone into "sequencing," the determination of the precise order of amino acid residues in a protein. Sequences of several hundreds of thousands of proteins and smaller peptides have been established and the number doubles each year.75 87 88 883 Most of these... 

On the other hand, pyrenyl-L-alanine 184 has also been used as a conformational probe in the characterization of an artificial 4-a-helix bundle protein.11,121 The 53-residue peptide 186 incorporating one residue of 184 in each of two different helical segments was synthesized by solid-phase synthesis using a segment condensation strategy and the oxime resin. Boc-pyrenyl-L-alanine 191 was coupled just like any other amino acid by the BOP/HOBt method in DMF. CD and fluorescence studies demonstrated that the two pyrene groups were in close proximity forming an excimer complex, which is possible only when the polypeptide chain folds into a 4-a-helix bundle structure. 

Glutathione helps to maintain the sulfhydryl groups of proteins in a reduced state. An enzyme, protein-disulfide reductase, catalyzes sulfhydryl disulfide interchanges between glutathione and proteins. The reductase is important in insulin breakdown and may catalyze the reassortment of disulfide bonds during polypeptide chain folding. 

Part 2, Protein Structure and Function, contains four chapters that relate to the structures and functions of proteins. In chapter 3, The Building Blocks of Proteins Amino Acids, Peptides, and Polypeptides, we discuss basic structural and chemical properties of amino acids, peptides and polypeptides. In chapter 4, The Three-Dimensional Structures of Proteins, we describe how and why polypeptide chains fold into long fibrous molecules in some cases, or into compact globular molecules in other cases. In chapter... 

We can make some generalizations about how proteins fold. For example, it is a stabilizing feature to get hydrogen-bonding portions of the chain in close proximity. Proteins typically fold with nonpolar side chains on the interior of the protein, away from water, and polar side chains on the outside of the protein, where they can interact with water molecules. In spite of these (gross) generalizations, however, the problem of how and why polypeptide chains fold into functional proteins remains one of the fundamental unsolved problems in physical biochemistry. 

The polypeptide chain folds up to form a specific shape (conformation) in the protein. This conformation is the three-dimensional arrangement of atoms in the structure and is determined by the amino acid sequence. There are four levels of structure in proteins primary, secondary, tertiary and, sometimes but not always, quaternary. 

A basic principle of protein chemistry is the central relationship between three-dimensional structure and activity. Unless the linear polypeptide chain folds into a particular three-dimensional configuration, the protein is inactive. As Fig. 2 illustrates, the active form of a protein is typically a highly convoluted, globular structure in which a particular small domain is the precise locus of interaction with reactant or binding ligand. 

Fig. 4. Ribbon diagram (81) of the polypeptide chain fold of the A. vinelandii Fe protein (15). The nucleotide binding sequence at the amino terminus of Fe protein is red. The 4Fe 4S cluster, ADP, and molybdate are represented by atomic models. 

Can a polypeptide chain fold into a regularly repeating structure In 1951, Linus Pauling and Robert Corey proposed two periodic structures called the a helix (alpha helix) and the p pleated sheet (beta pleated sheet). Subsequently, other structures such as the P turn and omega ( Q) loop were identified. Although not periodic, these common turn or loop structures are well defined and contribute with a helices and P sheets to form the final protein structure. 

Some polypeptide chains fold into two or more compact regions that may be connected by a flexible segment of polypeptide chain, rather like pearls on a string. These compact globular units, called domains, range in size from about 30 to 400 amino acid residues. For example, the extracellular part of CD4, the cell-surface protein on certain cells of the immune system to which the human immunodeficiency virus (HIV) attaches itself, comprises four similar domains of approximately 100 amino acids each (Figure 3.47). Often, proteins are found to have domains in common even if their overall tertiary structures are different. 

The polypeptide chain folds in a systematic way to give a specific three-dimensional structure for the protein. Kaj U. Linderstr0m-Lang described the hierarchical organization of protein structure in terms of four levels, diagrammed in Figure 12.22. ... 

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