Polypeptide chain fold

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. 

Large polypeptide chains fold into several domains... 

The molecular basis for quasi-equivalent packing was revealed by the very first structure determination to high resolution of a spherical virus, tomato bushy stunt virus. The structure of this T = 3 virus was determined to 2.9 A resolution in 1978 by Stephen Harrison and co-workers at Harvard University. The virus shell contains 180 chemically identical polypeptide chains, each of 386 amino acid residues. Each polypeptide chain folds into distinct modules an internal domain R that is disordered in the structure, a region (a) that connects R with the S domain that forms the viral shell, and, finally, a domain P that projects out from the surface. The S and P domains are joined by a hinge region (Figure 16.8). 

Figure 5.8 A schematic representation of the N-lobe polypeptide chain fold, showing the conformational change between open and closed forms of human lactoferrin. Reprinted with permission from Nature (Anderson et ah, 1990). Copyright (1990) Macmillan Magazines Limited.

Inouye, H., and Kirschner, D. A. (1998). Polypeptide chain folding in the hydrophobic core of hamster scrapie prion Analysis by X-ray diffraction. /. Struct. Biol. 122, 247-255. 

E. Haas, G. T. Montelione, C. A. McWherter, and H. A. Scheraga, Local structure in a tryptic fragment of performic acid oxidized ribonuclease A corresponding to a proposed polypeptide chain-folding initiation site detected by tyrosine fluorescence lifetime and proton magnetic resonance measurements, Biochemistry 26, 1672-1683 (1987). 

Such a polypeptide chain folding into two distinct domains could be correlated with the amino add sequence. The N-terminus of the polypeptide chain is located at an as yet unknown site of the head part and starts with the sequence Pyr.Glu-Ser-Ala-Cys-Thr-, the C-terminal region is located at the end of the tail and has the sequence -Pro-Tyr-TVr-Ser-Gln-Cys-Leu. From the total of 497 amino acids about 430 are located in the head part, where the chain is partially ordered in jS-structures. Ten disulfide bridges give stability and rigidity to this part of the molecule 24. The bridges interconnect the cysteine residues 4-50, 19-25, 61-71(7), 67-72(7), 138-397, 172-209(7), 176-210(7), 230-256, 238-243, and 261-331. The exact position of some... 

A. Structure of a 3-sheet. B. An antiparallel 3-sheet with the 3-strands represented as broad arrows. C. A parallel p-sheet formed from a single polypeptide chain folding back on itself. 

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... 

Figure 12-6 Drawing showing the overall polypeptide chain fold and relative positioning of the three structural domains of human pancreatic a-amylase. Also drawn are the locations of the calcium and chloride binding sites. Overlaid is the placement of a modified form of the inhibitor acarbose (p. 607) that binds in the active site cleft. MolScript drawing courtesy of G. Sidhu and G. Brayer.

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. 

Three polypeptide chains folded together to form a triple-helical cable... 

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