Structure, three-dimensional pleated-sheet

Proteins have four levels of structure. Primary structure describes a protein s amino acid sequence secondary structure describes how segments of the protein chain orient into regular patterns—either a-helix or /3-pleated sheet tertiary structure describes how the entire protein molecule coils into an overall three-dimensional shape and quaternary structure describes how individual protein molecules aggregate into larger structures. 

X-ray diffraction analysis reveals the three-dimensional structure of both IL-l molecules to be quite similar. Both are globular proteins, composed of six strands of antiparallel P pleated sheet forming a barrel that is closed at one end by a further series of P sheets. 

Figure 4.2 This three-dimensional image of a protein shows the many twists and folds in its structure. The coils, called alpha helices, and the ribbons, called beta pleated sheets, are generally determined by the amino acid sequence of the protein and how the amino acids in different parts form weak bonds with each other. The shape of a protein is often critical for its function.

A protein s primary structure is its amino acid sequence. Its secondary structure is the orientation of segments of the protein chain into a regular pattern, such as an a-helix or a P-pleated sheet. Its tertiary structure is the three-dimensional shape into which the entire protein molecule is coiled. 

The tertiary structure of a protein is its complete three-dimensional conformation. Think of the secondary structure as a spatial pattern in a local region of the molecule. Parts of the protein may have the a-helical structure, while other parts may have the pleated-sheet structure, and still other parts may be random coils. The tertiary structure includes all the secondary structure and all the kinks and folds in between. The tertiary structure of a typical globular protein is represented in Figure 24-17. 

The sequence of amino acids in the long chain defines the primary structure of a protein. A secondary structure is determined when several residues, linked by hydrogen bonds, conform to a given combination (e.g., the a-helix, pleated sheet, and P-turns). Tertiary structure refers to the three-dimensional folded conformation of a protein. This is the biologically active conformation (crystal structure). A quaternary structure can result when two or more individual proteins assemble into two or more polypeptide chains. Conjugated proteins are complexes of proteins with other biomolecules, such as glycoproteins (sugar-proteins). 

The three-dimensional structure of the PapD periplasmic chaperone that forms transient complexes with pilus subunit proteins has been solved by Holmgren and Branden (1989). PapD consists of two globular domains oriented in the shape of a boomerang (Fig. 2). Each domain is a /3-barrel structure formed by two antiparallel /8-pleated sheets that have a topology similar to an immunoglobulin fold. The relationship between PapD and other immunoglobulin-like proteins is discussed in Section IV,C. 

Second law of thermodynamics in any spontaneous process, there is always an increase in the entropy of the universe. (10.5) Secondary structure (of a protein) the three-dimensional structure of the protein chain (for example, a-helix, random coil, or pleated sheet). (22.6)... 

The three-dimensional conformations of localized regions of a protein are called its secondary structure. These regions arise due to hydrogen bonding between the N-H proton of one amide and C=0 oxygen of another. Two arrangements that are particularly stable are called the a-helix and the P-pleated sheet. 

In alpha-keratin, shown in Figure 5, the entire length of the protein has an a-helix structure. However, other proteins will have only sections that are a-helixes. Different sections of the same protein may have a pleated sheet secondary structure. These different sections of a protein can fold in different directions. These factors, combined with the inter-molecular forces acting between side chains give each protein a distinct three-dimensional shape. This shape is the tertiary structure of the protein. 

All enzyme molecules possess the primary, secondary, and tertiary structural characteristics of proteins (see Chapter 20). In addition, most enzymes also exhibit the quaternary level of structure. The primary structure, the linear sequence of amino adds linked through their a-carboxyl and a-amino groups by peptide bonds, is specific for each type of enzyme molecule. Each polypeptide cham is coiled up into three-dimensional secondary and tertiary levels of structure. Secondary structure refers to the conformation of limited segments of the polypeptide chain, namely a-helices, P-pleated sheets, random coils, and p-turns. The arrangement of secondary structural elements and amino acid side chain interactions that define the three-dimensional structure of the folded protein is referred to as its tertiary structure. In many cases biological activity, such as the catalytic activity of enzymes, requires two or more folded polypeptide chains (subunits) to associate to form a functional molecule. The arrangement of these subunits defines the quaternary structure. The subunits may be copies of the... 

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. 

Fig. 15. Three-dimensional structure of Anabaena ferredoxin in ribbon representation. The five strands of p-pleated sheet are labeled A to E. Figure source Holden, Jackson, Jacobson, Hurley, Tollin, Oh, Skjedal, Chae, Cheng, Xia and Markley (1993) Structure-function studies of[2Fe-2S] ferredoxins. J Bioenerg Biomembr 26 72.

Figure 4. Elements of secondary structure. (A) The hydrogen-bonding pattern of an a-helix. Hydrogen bonds (denoted by dashed lines) form between residues four positions away from each other in the helix. Unmarked atoms are hydrogens. (B) Two-dimensional projections of the hydrogen-bonding patterns of parallel and antiparallel pleated sheets. Parallel and antiparallel pleated-sheets have different three-dimensional structures.

The three-dimensional structure of bovine Cu,Zn-SOD has been studied by X-ray diffraction analysis at 2 A resolution (R2,T1). Each subunit is composed of eight antiparallel strands of (3-pleated sheet, which form a flattened cylinder, plus three external loops. Cu(II) and Zn(II) are bridged by His-61. Cu(II) is also coordinated to His-44, His-46, and His-118 (bovine sequence) in a square-planar geometry. Zn(II) is bridged to His-61, His-69, His-78, and Asp-81, and the geometry of the ligands is tetrahedral. 

Figure 3 Three-dimensional structure of DNase I. -Strands (marked by capital letters) are represented by arrows helices are represented by cylinders. Two six-stranded -pleated sheets consisting of strands E, F, C, A, P, N (sheet 1) and strands G, H, J, K, M, L (sheet 2) are packed against each other, forming the core of the enzyme. The flexible loop region connects -strands H and G. The carbohydrate side chain is attached to Asnl8 at the beginning of helix I. The disulfide bridge between Cysl73 and Cys209 is indicated. (From Ref. 23.)...

Biochemists distinguish four levels of the structural organization of proteins. In primary structure, the amino acid residues are connected by peptide bonds. The secondary structure of polypeptides is stabilized by hydrogen bonds. Prominent examples of secondary structure are a-helices and / -pleated sheets. Tertiary structure is the unique three-dimensional conformation that a protein assumes because of the interactions between amino acid side chains. Several types of interactions stabilize tertiary structure the hydrophobic effect, electrostatic interactions, hydrogen bonds, and certain covalent bonds. Proteins that consists of several separate polypeptide subunits exhibit quaternary structure. Both noncovalent and covalent bonds hold the subunits together. 

Proteins are composed of an amino acid backbone which defines their primary structure. The amino acid side chains hydrogen-bond to each other, creating areas of local order such as a helices and (3-pleated sheets. These types of arrangement are known as secondary structure. The overall folding of the molecule, which defines its three-dimensional shape, is known as the tertiary structure. Finally, some proteins, such as haemoglobin, are composed of more than one subunit the spatial arrangement of these subunits is known as the quarternary structure. 

Fig. 3. Peptide chain folding of a constant domain. The segments fxl-4 (unshaded) and fyi-3 (shaded) form two roughly parallel faces of antiparallel /3-pleated sheet linked by an intra-chain disulphide bridge (filled rectangle, Cys-I31-Cys-2(K) (Cyl, human IgGl). Cys-261-Cys-321 (C,2), Cys-367-Cys-425 (0 3)). Between the /3-pleated segments are other segments (bl-6) forming helices, bends and other structures. Segments fx3, fx4, fyl and b4 arc foreshortened in this three-dimensional representation after Beale and Feinstein [76].

Most fibrous proteins, such as silk, collagen, and the a-keratins, are almost completely insoluble in water. (Our skin would do us very little good if it dissolved in the rain.) The majority of cellular proteins, however, are soluble in the cell cytoplasm. Soluble proteins are usually globular proteins. Globular proteins have three-dimensional structures called the tertiary structure of the protein, which are distinct from their secondary structure. The pol)cpeptide chain with its regions of secondary structure, a-helix and fj-pleated sheet, further folds on itself to achieve the tertiary structure. 

We have shown that the shape of a protein is absolutely essential to its function. We have also mentioned that life can exist only within a rather narrow range of temperature and pH. How are these two concepts related As we will see, extremes of pH or temperature have a drastic effect on protein conformation, causing the molecules to lose their characteristic three-dimensional shape. Denaturation occurs when the organized structures of a globular protein, the a-helix, the p-pleated sheet, and tertiary folds become completely disorganized. However, it does not alter the primary structure. Denaturation of an a-helical protein is shown in Figure 19.17. 

As discussed previously (Section IV), residues 245-280 of bovine GDH display sequence homology with the residues comprising the coenzyme binding domain of the dehydrogenases of known three-dimensional structure and sequence. Moreover, the three residues to which a functional role has been attributed are all conserved in GDH and those residues, believed to lie facing the /3-pleated sheet regions, are either identical or functionally conserved in GDH when compared to other dehydrogenases. It seems likely, therefore, that residues 245-280 of bovine GDH comprise a portion of the adenylate subsite within the active site for coenzyme [subsite II in the Cross and Fisher model 309)]. 

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