Polypeptides helical structure

In dilute solutions the molecules are in continuous motion and assume different conformations in rapid succession (random coils). In the solid state many polymers have typical conformations, such as folded chains and helical structures. In polypeptides helical structures containing two or three chains (double and triple helices, respectively) are found. 

FIGURE 12.15 CD of a polypeptide —, helical structure —, disordered state. 

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 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... 

It can be assumed that the amino acids following this hinge region (Val 93 to Leu 447) are part of the head domain. The point of papain cleavage is at amino acid 82 27. TTie core part of the polypeptide chain is mainly folded in )3-sheets (34 %) and to a lesser extent (15 %) arranged in alpha-helical structures 7. In contrast with CBH I the core of CBH II possesses only 2 disulfide bridges (176-235 368-415) and four free sulfhydryl groups. Similarly to CBH I carboxyl functions are involved in the active center (Asp 175 and Glu 184) 28. 

Whereas the 3-pleated sheet provides a particularly nice and easily appreciated example of regular hydrogen bonding in polypeptide chains, the most common arrangement found in proteins is actually the a-helix (Figure 13.2). Do not worry about the a or P used in the nomenclature this merely signifies that the helical structure (a) was deduced earlier than that of the pleated sheet (P). 

There is another source of flexibility in polypeptide helices. It is the thermal fluctuations of bond rotation angles about their preferred a-helix values. This effect occurs without destroying the overall helical structure of the molecule and will become more important at higher temperature. 

Two major discoveries in 1953 were of crucial importance in the history of biochemistry. In that year James D. Watson and Francis Crick deduced the double-helical structure of DNA and proposed a structural basis for its precise replication (Chapter 8). Their proposal illuminated the molecular reality behind the idea of a gene. In that same year, Frederick Sanger worked out the sequence of amino acid residues in the polypeptide chains of the hormone insulin (Fig. 3-24), surprising many researchers who had long thought that elucidation of the amino acid sequence of a polypeptide would be a hopelessly difficult task. It quickly became evident that the nucleotide sequence in DNA and the amino acid sequence in proteins were somehow related. Barely a decade after these discoveries, the role of the nucleotide... 

Hydroxyproline and hydroxylysine Collagen contains hydroxy proline (hyp) and hydroxylysine (hyl), which are not present in most other proteins. These residues result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide chains (Figure 4.6). The hydroxylation is, thus, an example of posttranslational modification (see p. 440). Hydroxy proline is important in stabilizing the triple-helical structure of colla gen because it maximizes interchain hydrogen bond formation. 

What is the nature of the insoluble forms of the prion protein They are hard to study because of the extreme insolubility, but the conversion of a helix to (3 sheet seems to be fundamental to the process and has been confirmed for the yeast prion by X-ray diffraction.11 It has been known since the 1950s that many soluble a-helix-rich proteins can be transformed easily into a fibrillar form in which the polypeptide chains are thought to form a P sheet. The chains are probably folded into hairpin loops that form an antiparallel P sheet (see Fig. 2-ll).ii-11 For example, by heating at pH 2 insulin can be converted to fibrils, whose polarized infrared spectrum (Fig. 23-3A) indicates a cross-P structure with strands lying perpendicular to the fibril axis >mm Many other proteins are also able to undergo similar transformation. Most biophysical evidence is consistent with the cross-P structure for the fibrils, which typically have diameters of 7-12 rnn."-11 These may be formed by association of thinner 2 to 5 nm fibrils.00 However, P-helical structures have been proposed for some amyloid fibrils 3 and polyproline II helices for others. 1 11... 

Spin-lattice relaxation times and 13C chemical shifts were used to study conformational changes of poly-L-lysine, which undergoes a coil-helix transition in a pH range from 9 to 11. In order to adopt a stable helical structure, a minimum number of residues for the formation of hydrogen bonds between the C = 0 and NH backbone groups is necessary therefore for the polypeptide dodecalysine no helix formation was observed. Comparison of the pH-dependences of the 13C chemical shifts of the carbons of poly-L-lysine and (L-Lys)12 shows very similar values for both compounds therefore downfield shifts of the a, / and peptide carbonyl carbons can only be correlated with caution with helix formation and are mainly due to deprotonation effects. On the other hand, a sharp decrease of the 7] values of the carbonyl and some of the side chain carbons is indicative for helix formation [854]. 

Figure 25-16 A model of myoglobin to show the way in which the polypeptide chain is coiled and folded. The shaded sections correspond to regions in which the chain is coiled into an a helix. Each fold, and the regions near the C-terminus and the /V-terminus, represent discontinuities in the helical structure. The position of the heme group is represented by the disoiike shape.

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.)... 

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