Protein structure nonrepetitive

Richardson JS, Getzoff ED, Richardson DC (1978) The / -bulge a common small unit of nonrepetitive protein structure. Proc Natl Acad Sci USA 75 2574-2578... 

In contrast to the well-ordered but nonrepetitive coil structures, there are also genuinely disordered regions in proteins, which are either entirely absent on electron density maps or which appear with a much lower and more spread out density than the rest of the protein. The disorder could either be caused by actual motion, on a time scale of anything shorter than about a day, or it could be caused by having multiple alternative conformations taken up by the different mole-... 

Approximately one half of an average globular protein is organized into repetitive structures, such as the a-helix and/or 3-sheet. The remainder of the polypeptide chain is described as having a loop or coil conformation. These nonrepetitive secondary structures are not... 

Fig. 7.8. Ribbon drawing showing the arrangement of secondary structures into a three-dimensional pattern in domain 1 of lactate dehydrogenase. The individual polyjjeptide strands in the six-stranded P-sheet are shown with arrows. Different strands are connected by helices and by nonrepetitive structures (mrns, coils and loops), shown in blue. This domain is the nucleotide binding fold. NAD is bound to a site created by the helices (upper left of figure.) (Modified from Richardson JS. Adv Protein Chem. The anatomy and taxonomy of protein structure 1981 34 167).

The right-handed helices and extended P strands are the only protein conformations in which the same ( ), / angles repeat for each consecntive residne as regular, repetitive structures. The remaiiung portions of protein structures are made up of well-ordered but nonrepetitive conformations referred to as coils. Nonrepetitive structure involve both backbone hydrogen bonds and freqnent side chain-to-main chain hydrogen bonds. The reliance on specific side chain interactions is characteristic for nonrepetitive structures. The nonrepetitive stmctnre consists of two general types connection or loop and turn. 

Nonrepetitive but well-defined structures of this type form many important features of enzyme active sites. In some cases, a particular arrangement of coil structure providing a specific type of functional site recurs in several functionally related proteins. The peptide loop that binds iron-sulfur clusters in both ferredoxin and high potential iron protein is one example. Another is the central loop portion of the E—F hand structure that binds a calcium ion in several calcium-binding proteins, including calmodulin, carp parvalbumin, troponin C, and the intestinal calcium-binding protein. This loop, shown in Figure 6.26, connects two short a-helices. The calcium ion nestles into the pocket formed by this structure. 

Based on the same principle, there are monomeric / -helical proteins that carry at their extremities a cluster of helical or nonrepetitive structures that could act as a capping element covering their exposed ends (Emsley et al., 1996 Lietzke et al, 1994 Petersen et al, 1997 Steinbacher et al, 1994). For example, the last 40 residues of pectate lyase C form a large loop that partially covers the surface of the /Hielix (Yoder et al, 1993). The fibrous (or otherwise elongated) domain of these natural /f-stranded proteins is not stable in isolation, as for example in the case of the P22 tailspike where bacterially expressed isolated /Hielix domain, at high concentrations, forms fibrous aggregates that bind Congo red (Schuler et al, 1999). 

Globular proteins are constructed by combining secondary structural elements (a-helices, 3-sheets, nonrepetitive sequences). These form primarily the core region—that is, the interior of the molecule. They are connected by loop regions (for example, 3-bends) at the surface of the protein. Supersecondary structures are usually pro duced by packing side chains from adjacent secondary structural elements close to each other. Thus, for example, a-helices and 3-sheets that are adjacent in the amino acid sequence are also usu ally (but not always) adjacent in the final, folded protein. Some of the more common motifs are illustrated in Figure 2.8. 

Figure 6.1. The role of HMW subunits in gluten structure and functionality. Amino acid sequences derived from direct analysis of purified proteins and the isolation and sequencing of corresponding genes show that the proteins have highly conserved structures, with repetitive domains flanked by shorter nonrepetitive domains containing cysteine residues (SH) available for formation of interchain disulphide bonds. Molecular modelling indicates that the individual repetitive domains form a loose spiral structure (bottom right) while SPM shows that they interact by noncovalent forces to form fibrils (centre right). Includes figures from Parchment et al. (2001) and Humphries et al. (2000).

In contrast to a-helices, /1-sheets do not involve interactions between amino acids close in sequence. Amino acids that interact within / -sheets are often found widely separated in the primary structure. Therefore, / -sheet formation needs structures that bring two polypeptide segments into close proximity. This is achieved via reverse turn structures [96]. Turns are aperiodic or nonrepetitive elements of secondary structure which mediate the folding of the polypeptide chain into a compact tertiary structure. Turns usually occur on the environment-exposed surface of proteins [97,98], Reverse turns play an important role in polypeptide function, both as elements of structure as well as modulators of bioactivity [99]. Among the reverse turns found in proteins the /1-turn is the most relevant [100]. /1-Turns comprise four amino acid residues (i to i+3) forming an almost complete 180° turn in the direction of the peptide chain [101,102]. 

Telomeres. The DNA sequences at the chromosome ends have a TG-rich strand, such as the (TTGGGG)5o 7o Tetrahymemy and the (TTAGGG) of both human and trypanosome chromosomes. The complementary DNA strand is CA-rich. The S. cereaisiae telomers have 350 base pairs containing the sequences (TGj 3 / C3 3A) as well as one or more copies of a 6.7-kb nonrepetitive sequence and other elements. In many species the repetitive telo-meric sequences have 3 poly(G) tails at the ends of the DNA molecules. These tails are able to form G quartet structures (Fig. 5-26 and Chapter 5, Section C,4). A variety of telomere-binding proteins have been isolated. " Some of these bind to G quartet struc-... 

Helices and pleated sheets account for only about one-half of the structure of the average globular protein. The remaining polypeptide segments have what is called a coil or loop conformation. These nonrepetitive structures are not random they are just more difficult to describe. Globular proteins also have stretches, called reverse turns or j8 bends, where the polypeptide chain abruptly changes direction. These often connect successive strands of /3 sheets and almost always occur at the surface of proteins. 

Globular proteins have a nonrepetitive sequence. They range in size from 100 to several hundred residues and adopt a unique compact structure. In globular proteins, nonpolar amino acid side chains have a tendency to cluster together to form the interior, hydrophobic core of the proteins, whereas the... 

Generally, less than half of the protein s backbone is arranged in a defined secondary structure—an a-helix or a j8-pleated sheet (Figure 22.10). Most of the rest of the protein, though highly ordered, is nonrepetitive and therefore difficult to describe. Many of these ordered polypeptide fragments are said to be in coil or loop conformations. 

Many proteins contain secondary structure that cannot be described as either helix or turn. This is typically classified as turn, loop, or random coil. These sections of the polypeptide chain are characterized by nonrepetitive conformational angles however, this does not necessarily imply that these residues are less stable or less well ordered than the regular secondary structural elements. Many active site residues and components critical for ligand recognition reside in loops or random coil and adopt an exquisitely well-defined conformation. 

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