Polypeptides three-dimensional shapes

When the polypeptide chains of protein molecules bend and fold in order to assume a more compact three-dimensional shape, a tertiary (3°) level of structure is generated (Figure 5.9). It is by virtue of their tertiary structure that proteins adopt a globular shape. A globular conformation gives the lowest surface-to-volume ratio, minimizing interaction of the protein with the surrounding environment. 

Each protein has a unique three-dimensional shape called its tertiary structure. The tertiary structure is the result of the bends and folds that a polypeptide chain adopts to achieve the most stable structure for the protein. As an analogy, consider the cord in Figure 13-39 that connects a computer to its keyboard. The cord can be pulled out so that it is long and straight this corresponds to its primary structure. The cord has a helical region in its center this is its secondary structure. In addition, the helix may be twisted and folded on top of itself This three-dimensional character of the cord is its tertiary structure. 

There are three potential methods by which a protein s three-dimensional structure can be visualized X-ray diffraction, NMR and electron microscopy. The latter method reveals structural information at low resolution, giving little or no atomic detail. It is used mainly to obtain the gross three-dimensional shape of very large (multi-polypeptide) proteins, or of protein aggregates such as the outer viral caspid. X-ray diffraction and NMR are the techniques most widely used to obtain high-resolution protein structural information, and details of both the principles and practice of these techniques may be sourced from selected references provided at the end of this chapter. The experimentally determined three-dimensional structures of some polypeptides are presented in Figure 2.8. 

The three-dimensional shape of a polypeptide chain or a portion of a chain is known as the secondary structure. In its simplest form the fully extended polypeptide chain would show a structure similar to that indicated in Figure 11.2(a). However, it often assumes a helical structure similar to that shown in Figure 11.2(b) which is stabilized by intra-chain hydrogen... 

The secondary structure of a protein is the three-dimensional shape of a polypeptide chain. 

As has been described, CD is one of the few spectroscopic techniques sensitive to the structural parameters that define and guide the three-dimensional shape of a biologically active entity. This important structural information, obtained on a time-resolved basis in the same time domain as the biological event under study, is an extremely important advance that will have wide application in biophysical studies of proteins, polypeptides and other biologically significant species. 

The properties of a protein depend primarily on its three-dimensional structure. The sequence of amino acids in the polypeptide chain is termed its primary structure. Its secondary structure is the shape of the backbone polypeptide chain. Remember that each amide group is planar, but the chain can have various conformations about the bond between the a-carbon and the nitrogen. The tertiary structure is the overall three-dimensional shape of the protein, including the conformations of the side chains. 

The shape adopted when two or more folded polypeptide chains aggregate into one protein complex is called the quaternary structure of the protein. Each individual polypeptide chain is called a subunit of the overall protein. Hemoglobin, for example, consists of two a and two P subunits held together by intermolecular forces in a compact three-dimensional shape. The unique function of hemoglobin is possible only when all four subunits are together. 

As a polypeptide is synthesized in a cell, its amino acid sequence might appear random (i.e., a few hydrophilic acids, followed by several lipophilic acids, then a number of hydrophilic ones, and so on). However, as the polypeptide folds and coils into a three-dimensional shape, it becomes apparent that this structure is controlled by the sequence of R groups. The polypeptide chain folds so that the... 

A variety of membrane-bound proteins are of vital interest to the medical and nutritional ientist, because defects or changes in these proteins can cause such problems as lactose intolerance, cardiovascular disease, cystic fibrosis, and diabetes. Sucrase-isomaltase, an enzyme of the small intestine, is a membrane-bound protein, bound to the plasma membrane of the cnterocyte (gut cell). Part of the production of this enzyme is depicted in Figure 1,26. in Step 1, the polypeptide chain is polymerized on the ribosome (shown in black). In Step 2, part of the amino add chain near the N terminus crosses the membrane of the ER into the lumen but some of the amino acids at the N terminus remain outside. Step 3 shows the protein assuming a three-dimensional shape within the lumen both the C and N... 

Proteins are not just long polypeptide chains. Because of the interactions of the side chains and other forces, each protein usually folds up into a unique shape. The three-dimensional shape that the chain forms gives characteristic properties to each protein. If a polypeptide chain folds into the wrong shape, it can function differently. It may also be unable to carry out its biological role. The levels of protein structure are shown in Table 3. 

The form and function of a protein depends on its three-dimensional shape, which itself depends on the amino acid sequence in the polypeptide chain. 

The folding of polypeptide chains into both helices (left) and sheets (right) involves amino acids that are fairly close together in the chain being held in position by hydrogen bonds. Other interactions among the various side chains are not shown here but play an important role in determining the three-dimensional shape of a polypeptide. 

Tertiary structure describes the overall three-dimensional shape of the polypeptide, including the way in which a helix and P sheet regions fold together to shape the macromolecule. 

The tertiary structure is the overall three-dimensional shape into which the a-helix or 8-pleated sheet folds as a result of interactions between residues far apart in the primary structure. Proteins may also have a quaternary structure, which describes how polypeptide chains stack together in a multichain protein. 

What happens when the three-dimensional structure of a protein is disrupted Think of the difference between the consistency of a raw egg white and that of a hard-boiled egg. When the forces holding a polypeptide chain in its three-dimensional shape are broken, the protein is unfolded in a process called denaturation. High temperatures can denature proteins, which is why cooking foods that contain proteins results in the proteins denaturation. Denatured proteins form the solid white of a hard-boiled egg. In addition, proteins can be denatured by extremes in pH, mechanical agitation, and chemical treatments. When egg whites are beaten, the proteins are denatured, as shown in Figure 19.4. Because the folded shape of a protein is essential for its function, denaturation of a protein results in loss of its function. This is one reason why organisms can live only in a narrow temperature and pH range. 

Biochemists have distinguished several levels of the structural organization of proteins. Primary structure, the amino acid sequence, is specified by genetic information. As the polypeptide chain folds, it forms certain localized arrangements of adjacent amino acids that constitute secondary structure. The overall three-dimensional shape that a polypeptide assumes is called the tertiary structure. Proteins that consist of two or more polypeptide chains (or subunits) are said to have a quaternary structure. 

Describe the problems associated with determining a polypeptide s finale three-dimensional shape using its primary structure as a guide. 

Interactions of secondary structures within a single polypeptide chain generate tertiary structuresthe complex three-dimensional shapes of proteins. Interactions between separate polypeptide chains in the same protein generate a quaternary structure, which mediates interactions between the subunits. Tertiary and quaternary structures may be stabilized by disulfide bridges between cysteine residues, forming cystines. 

Nucleic acids can play roles farbeyond merely harbouring the coding information for proteins. Single-stranded nucleic acids can fold into intricate structures capable of molecular recognition and even catalysis. Three-dimensional structures are specified by the primary structure, namely the deoxynucleotide (or nucleotide, for RNA) sequence (5 - 3, by analogy to the situation in which the amino-acid residue sequence determines the three-dimensional structures of polypeptides. In nature, transfer RNAs (tRNAs) use their three-dimensional shape for molecular recognition, while some ribosomal RNAs (rRNAs) are able to catalyse crucial steps even within the protein synthetic pathways themselves. 

Cysteine contains the sulfhydryl (—SH) group in its side chain. It can therefore form disulfide linkages (—S—S—) with other cysteine molecules in the same polypeptide chain. This produces a kink or a knot in the chain, which leads to the tertiary structure (three-dimensional shape). For example, cysteine is responsible for the curling of hair. 

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