Helical polypeptide chain structures

Tropomyosin and troponin are proteins located in the thin filaments, and together with Ca2+, they regulate the interaction of actin and myosin (Fig. 43-3) [5]. Tropomyosin is an a-helical protein consisting of two polypeptide chains its structure is similar to that of the rod portion of myosin. Troponin is a complex of three proteins. If the tropomyosin-troponin complex is present, actin cannot stimulate the ATPase activity of myosin unless the concentration of free Ca2+ increases substantially, while a system consisting solely of purified actin and myosin does not exhibit any Ca2+ dependence. Thus, the actin-myosin interaction is controlled by Ca2+ in the presence of the regulatory troponin-tropomyosin complex [6]. 

Transfer of information from DNA to protein. The nucleotide sequence in DNA specifies the sequence of amino acids in a polypeptide. DNA usually exists as a two-chain helical structure. The information contained in the nucleotide sequence of only one of the DNA chains is used to specify the nucleotide sequence of the messenger RNA molecule (mRNA). This sequence information is used in polypeptide synthesis. A three-nucleotide sequence in the mRNA molecule codes for a specific amino acid in the polypeptide chain. (Illustration copyright by Irving Geis. Reprinted by permission.)... 

Primary structure refers to the amino acid sequence, the simplest level of structure. Secondary structure is any regular local structure of a segment of a polypeptide chain, such as a helical fold or an extended hydrogen-bonded pair of strands. Tertiary structure is the overall topology of the folded polypeptide chain. Quaternary structure describes the aggregation of folded polypeptides with each other by means of specific interactions, such as the aggregation of subunits to... 

Figure 25 The structures of the anaerobic cobaltochelatases CbiK and CbiX. CbiK is a monomeric enzyme derived from a single polypeptide chain (helices in blue, purple sheets). CbiX is a dimeric enzyme, where each monomer (green helices/ orange sheets) corresponds to one of the domains observed in CbiK. It has been suggested therefore that CbiK arose from a gene duplication and fusion event of cbiX.

The first question to be answered is that as to the nature of the core of the three-chain -hehcal molecule—the part of the molecule closest to the axis. It is important for stability of the molecule that atoms be well packed together, and the problem of packing atoms together is a more difiicult one to solve in the neighborhood of the axis than at a distance away from the axis, where there is a larger distance between an atom and the equivalent atom in the next unit. (An example of a helical structure which seems to satisfy all of the structural requirements except that of close packing of atoms in the region near the helical axis is the 5.2-residue helix of polypeptide chains. This structure seems not to be represented in proteins, whereas... 

Figure 16.21 The a-helical structure of a polypeptide chain. The structure is held in position by intramolecular hydrogen bonds, shown as dotted lines. For color key, see Figure 16.19.

Figure 1.1 The amino acid sequence of a protein s polypeptide chain is called Its primary structure. Different regions of the sequence form local regular secondary structures, such as alpha (a) helices or beta (P) strands. The tertiary structure is formed by packing such structural elements into one or several compact globular units called domains. The final protein may contain several polypeptide chains arranged in a quaternary structure. By formation of such tertiary and quaternary structure amino acids far apart In the sequence are brought close together in three dimensions to form a functional region, an active site.

Parvalbumin is a muscle protein with a single polypeptide chain of 109 amino acids. Its function is uncertain, but calcium binding to this protein probably plays a role in muscle relaxation. The helix-loop-helix motif appears three times in this structure, in two of the cases there is a calcium-binding site. Figure 2.13 shows this motif which is called an EF hand because the fifth and sixth helices from the amino terminus in the structure of parvalbumin, which were labeled E and F, are the parts of the structure that were originally used to illustrate calcium binding by this motif. Despite this trivial origin, the name has remained in the literature. 

Secondary structure occurs mainly as a helices and p strands. The formation of secondary structure in a local region of the polypeptide chain is to some extent determined by the primary structure. Certain amino acid sequences favor either a helices or p strands others favor formation of loop regions. Secondary structure elements usually arrange themselves in simple motifs, as described earlier. Motifs are formed by packing side chains from adjacent a helices or p strands close to each other. 

Domains are formed by different combinations of secondary structure elements and motifs. The a helices and p strands of the motifs are adjacent to each other in the three-dimensional structure and connected by loop regions. Sequentially adjacent motifs, or motifs that are formed from consecutive regions of the primary structure of a polypeptide chain, are usually close together in the three-dimensional structure (Figure 2.20). Thus to a first approximation a polypeptide chain can be considered as a sequential arrangement of these simple motifs. The number of such combinations found in proteins is limited, and some combinations seem to be structurally favored. Thus similar domain structures frequently occur in different proteins with different functions and with completely different amino acid sequences. 

Polypeptide chains are folded into one or several discrete units, domains, which are the fundamental functional and three-dimensional structural units. The cores of domains are built up from combinations of small motifs of secondary structure, such as a-loop-a, P-loop-p, or p-a-p motifs. Domains are classified into three main structural groups a structures, where the core is built up exclusively from a helices p structures, which comprise antiparallel p sheets and a/p structures, where combinations of p-a-P motifs form a predominantly parallel p sheet surrounded by a helices. 

Pauling, L., Corey, R.B., Branson, H.R. The structure of proteins two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl. Acad. Sd. USA 37 205-211, 1951. 

Figure 3.6 Four-helix bundles frequently occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the three-dimensional structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core, (a) Schematic representation of the path of the polypeptide chain in a four-helrx-bundle domain. Red cylinders are a helices, (b) Schematic view of a projection down the bundle axis. Large circles represent the main chain of the a helices small circles are side chains. Green circles are the buried hydrophobic side chains red circles are side chains that are exposed on the surface of the bundle, which are mainly hydrophilic.

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

Figure 4.7 Two of the enzymatic activities involved in the biosynthesis of tryptophan in E. coli, phosphoribosyl anthranilate (PRA) isomerase and indoleglycerol phosphate (IGP) synthase, are performed by two separate domains in the polypeptide chain of a bifunctional enzyme. Both these domains are a/p-barrel structures, oriented such that their active sites are on opposite sides of the molecule. The two catalytic reactions are therefore independent of each other. The diagram shows the IGP-synthase domain (residues 48-254) with dark colors and the PRA-isomerase domain with light colors. The a helices are sequentially labeled a-h in both barrel domains. Residue 255 (arrow) is the first residue of the second domain. (Adapted from J.P. Priestle et al., Proc.

A, B, and C, surrounded by a helices. The polypeptide chain is colored in sections from the N-terminus to facilitate following the chain tracing in the order green, blue, yellow, red and pink. The red region corresponds to the active site loop in the serpins which in ovalbumin is protruding like a handle out of the main body of the structure. (Adapted from R.W. Carrell et al.. Structure 2 257-270, 1994.)... 

Figure 6.25 Schematic diagram of the structure of one dimer of phosphofructokinase. Each polypeptide chain is folded Into two domains (blue and red, and green and brown), each of which has an oi/p structure. Helices are labeled A to M and p strands 1 to 11 from the amino terminus of one polypeptide chain, and respectively from A to M and 1 to 11 for the second polypeptide chain. The binding sites of substrate and effector molecules are schematically marked In gray. The effector site of one subunit is linked to the active site of the other subunit of the dimer through the 6-F loop between helix F and strand 6. (Adapted from T. Schlrmer and P.R. Evans, Nature 343 140-145, 1990.)...

Figure 8.3 The DNA-binding protein Cro from bacteriophage lambda contains 66 amino acid residues that fold into three a helices and three P strands, (a) A plot of the Ca positions of the first 62 residues of the polypeptide chain. The four C-terminal residues are not visible in the electron density map. (b) A schematic diagram of the subunit structure. a helices 2 and 3 that form the helix-turn-helix motif ate colored blue and red, respectively. The view is different from that in (a), [(a) Adapted from W.F. Anderson et al., Nature 290 754-758, 1981. (b) Adapted from D. Ohlendorf et al., /. Mol. Biol. 169 757-769, 1983.]...

The polypeptide chain of the 92 N-terminal residues is folded into five a helices connected by loop regions (Figure 8.6). Again the helices are not packed against each other in the usual way for a-helical structures. Instead, a helices 2 and 3, residues 33-52, form a helix-turn-helix motif with a very similar structure to that found in Cro. 

The L and the M subunits are firmly anchored in the membrane, each by five hydrophobic transmembrane a helices (yellow and red, respectively, in Figure 12.14). The structures of the L and M subunits are quite similar as expected from their sequence similarity they differ only in some of the loop regions. These loops, which connect the membrane-spanning helices, form rather flat hydrophilic regions on either side of the membrane to provide interaction areas with the H subunit (green in Figure 12.14) on the cytoplasmic side and with the cytochrome (blue in Figure 12.14) on the periplasmic side. The H subunit, in addition, has one transmembrane a helix at the car-boxy terminus of its polypeptide chain. The carboxy end of this chain is therefore on the same side of the membrane as the cytochrome. In total, eleven transmembrane a helices attach the L, M, and H subunits to the membrane. 

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