Polypeptide a-helix

As is known, the polypeptide a-helix molecules are rod-shaped if the helical internal structures are smeared out. Therefore, we may expect a phase separation in their solutions also. Indeed, Robinson (27) found in 1956 a phase separation in several solutions of the a-helix, poly-y-benzyl-L-glutamate, in which the second phase, separated out as small droplets, showed an optical birefringence. ITie critical concentration is of course a function of the molecular length. 

Fig. 2 Illustration of the basic secondary structure motifs of polypeptides a-helix (left) and antiparallel ff-sheet (r/g/it)...

Helices are repeating coiled structures commonly found in polypeptides. A helix can be described using the following important terms (Figure 4B.2). 

Peptide CD studies have revealed the importance of the amide n-w transition in amide spectra. This transition which contributes an important CD band at 222 nm in the polypeptide a helix spectrum also appears in the CD spectra of N-acetyl... 

Block copolymers containing a biologically active, polypeptide block were originally studied as models for biological membranes. The variety of conformations of polypeptides (a-helix, )3-sheet, and random coil) were expected to produee new copolymers of technical interest [10]. 

Fig.11.4D The polypeptide a-helix, with poly-L-alanine as an example. There are 3.6 residues per turn and a translation along the helix of 150 pm per residue, giving a pitch of544 pm. The diameter (ignoring side chains) is about 600 pm.

We want to be able to deduce the conformation of a polymer in solution from its measured circular dichroism spectrum. For a linear polymer each ordered conformation must be a helix. The limiting cases for a helix are a straight line and a circle. A helix of identical residues is characterized by very few parameters. These are the radius of the helix, the rise per residue (the distance along the helix axis) and the number of residues per turn. A few examples will make this clear. A planar, all trans polyene will have a radius of zero (the helix is a straight line), a rise of 1.44 A and one residue per turn. A polypeptide a-helix has a radius of 2.28 A at the a-carbon, a rise per residue of 1.50 A and 3.6 residues per turn. One strand of a polynucleotide helix in the Watson-Crick B-form of DNA has a radius of 5.72 A at Cr of deoxyribose, a rise per residue of 3.4 A and 10 residues per turn. 

In Forges, Professor Blout has recalled that the chirality of helical conformation did not escape the attention of Pasteur himself. To go beyond the first steps of a helix long chains are needed they were then unknown and Pasteur exemplified his idea by the image of a spiral staircase. This was long before the discovery of the macromolecular polypeptide a-helix based on X-ray studies by Pauling and Bragg, and the identification of the DNA double helix by Watson and Crick. The systematic investigations on optical activity, ORD and CD related to these ordered conformations in biopolymer solutions have followed. 

Section 27 19 Two secondary structures of proteins are particularly prominent The pleated sheet is stabilized by hydrogen bonds between N—H and C=0 groups of adjacent chains The a helix is stabilized by hydrogen bonds within a single polypeptide chain... 

Fig. 5. Protein folding. The unfolded polypeptide chain coUapses and assembles to form simple stmctural motifs such as -sheets and a-hehces by nucleation-condensation mechanisms involving the formation of hydrogen bonds and van der Waal s interactions. Small proteins (eg, chymotrypsin inhibitor 2) attain their final (tertiary) stmcture in this way. Larger proteins and multiple protein assembhes aggregate by recognition and docking of multiple domains (eg, -barrels, a-helix bundles), often displaying positive cooperativity. Many noncovalent interactions, including hydrogen bonding, van der Waal s and electrostatic interactions, and the hydrophobic effect are exploited to create the final, compact protein assembly. Further stmctural...

Fig. 2. Protein secondary stmcture (a) the right-handed a-helix, stabilized by intrasegmental hydrogen-bonding between the backbone CO of residue i and the NH of residue t + 4 along the polypeptide chain. Each turn of the helix requires 3.6 residues. Translation along the hehcal axis is 0.15 nm per residue, or 0.54 nm per turn and (b) the -pleated sheet where the polypeptide is in an extended conformation and backbone hydrogen-bonding occurs between residues on adjacent strands. Here, the backbone CO and NH atoms are in the plane of the page and the amino acid side chains extend from C ...

The hairpin motif is a simple and frequently used way to connect two antiparallel p strands, since the connected ends of the p strands are close together at the same edge of the p sheet. How are parallel p strands connected If two adjacent strands are consecutive in the amino acid sequence, the two ends that must be joined are at opposite edges of the p sheet. The polypeptide chain must cross the p sheet from one edge to the other and connect the next p strand close to the point where the first p strand started. Such CTossover connections are frequently made by a helices. The polypeptide chain must turn twice using loop regions, and the motif that is formed is thus a p strand followed by a loop, an a helix, another loop, and, finally, the second p strand. 

Hemoglobin is a tetramer built up of two copies each of two different polypeptide chains, a- and (5-globin chains in normal adults. Each of the four chains has the globin fold with a heme pocket. Residue 6 in the p chain is on the surface of a helix A, and it is also on the surface of the tetrameric molecule (Figure 3.13). 

For example, each subunit of the dimeric glycolytic enzyme triosephos-phate isomerase (see Figure 4.1a) consists of one such barrel domain. The polypeptide chain has 248 residues in which the first p strand of the barrel starts at residue 6 and the last a helix of the barrel ends at residue 246. In contrast, the subunit of the glycolytic enzyme pyruvate kinase (Figure 4.5), which was solved at 2.6 A resolution in the laboratory of Ffilary Muirhead, Bristol University, UK, is folded into four different domains. The polypeptide chain of this cat muscle enzyme has 530 residues. In Figure 4.5, residues 1-42... 

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. 

Figure 8.21 Richardson-type diagram of the structure of one suhunit of the lac repressor. The polypeptide chain is arranged in four domains, an amino terminal DNA-hinding domain (red) with a helix-tum-helix motif, a hinge helix (purple), a large core domain which has two subdomains (green and hlue) and a C-terminal a helix. (Adapted from M. Lewis et al.. Science 271 1247-1254, 1996.)...

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

Figure 9.22 Most tumorigenic mutations of pS3 are found in the regions of the polypeptide chain that are involved in protein-DNA interactions. These regions are loops L2 (green) and L3 (red) and a region called LSH (blue) which comprises part of p strand 9 as well as the C-terminal a helix.

Figure 12.1 Four different ways in which protein molecules may be bound to a membrane. Membrane-bound regions are green and regions outside the membrane are red. Alpha-helices are drawn as cylinders and P strands as arrows. From left to right are (a) a protein whose polypeptide chain traverses the membrane once as an a helix, (b) a protein that forms several transmembrane a helices connected by hydrophilic loop regions,...

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. 

FIGURE 5.8 Two structural motifs that arrange the primary structure of proteins into a higher level of organization predominate in proteins the a-helix and the /3-pleated strand. Atomic representations of these secondary structures are shown here, along with the symbols used by structural chemists to represent them the flat, helical ribbon for the a-helix and the flat, wide arrow for /3-structures. Both of these structures owe their stability to the formation of hydrogen bonds between N—H and 0=C functions along the polypeptide backbone (see Chapter 6). 

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