A-Helix, in proteins

The a-helix is the most abundant secondary structural element, determining the functional properties of proteins as diverse as a-keratin, hemoglobin and the transcription factor GCN4. The average length of an a-helix in proteins is approximately 17 A, corresponding to 11 amino acid residues or three a-helical turns. In short peptides, the conformational transition from random coil to a-helix is usually entropically disfavored. Nevertheless, several methods are known to induce and stabilize a-helical conformations in short peptides, including ... 

A direct confirmation of the occurrence of the a-helix in proteins was obtained in the 2 A Fourier synthesis of myoglobin by Kendrew et al. (1960). The screw-sense of the a-helix was found to be right-handed in all the helical sections of the molecule. 

Apart from the a-helix in proteins (Fig. 3, Table 2), a helical structure is also found for the conformation of the structural subunits of collagen and tropocollagen three screw-shaped polypeptide chains, constructed alternately mainly from glycine, proline and hydroxyproline, are wound around each other and form a rigid cable. The single strands of this helix form a structure by far wider open than those known in the polypeptide helix series. Other molecules which are structurally similar to collagen are found in other areas where mechanical endurance is important. Myosin... 

Conformational free energy simulations are being widely used in modeling of complex molecular systems [1]. Recent examples of applications include study of torsions in n-butane [2] and peptide sidechains [3, 4], as well as aggregation of methane [5] and a helix bundle protein in water [6]. Calculating free energy differences between molecular states is valuable because they are observable thermodynamic quantities, related to equilibrium constants and... 

A coiled a helix in a protein IS another example of a supercoil... 

The most common location for an a helix in a protein structure is along the outside of the protein, with one side of the helix facing the solution and the other side facing the hydrophobic interior of the protein. Therefore, with 3.6 residues per turn, there is a tendency for side chains to change from hydrophobic to hydrophilic with a periodicity of three to four residues. Although this trend can sometimes be seen in the amino acid sequence, it is not strong enough for reliable stmctural prediction by itself, because residues that face the solution can be hydrophobic and, furthermore, a helices can be either completely buried within the protein or completely exposed. Table 2.1 shows examples of the amino acid sequences of a totally buried, a partially buried, and a completely exposed a helix. 

These genetic experiments clearly demonstrated that the proposed structural model for the binding of these proteins to the phage operators was essentially correct. The second a helix in the helix-turn-helix motif is involved in recognizing operator sites as well as in the differential selection of operators by P22 Cro and repressor proteins. However, a note of caution is needed many other early models of DNA-protein interactions proved to be misleading, if not wrong. Modeling techniques are more sophisticated today but are still not infallible and are certainly not replacements for experimental determinations of structure. 

An a helix in the first zinc motif provides the specific protein-DNA interactions... 

Figure 18.11 Electron-density maps at different resolution show more detail at higher resolution, (a) At low resolution (5.0 A) individual groups of atoms are not resolved, and only the rodlike feature of an

Less commonly, an a-helix can be completely buried in the protein interior or completely exposed to solvent. Citrate synthase is a dimeric protein in which a-helical segments form part of the subunit-subunit interface. As shown in Figure 6.24, one of these helices (residues 260 to 270) is highly hydrophobic and contains only two polar residues, as would befit a helix in the protein core. On the other hand. Figure 6.24 also shows the solvent-exposed helix (residues 74 to 87) of cahnodulln, which consists of 10 charged residues, 2 polar residues, and only 2 nonpolar residues. 

The structure of the major trimeric LHCII complex has been recently obtained at 2.72 A (Figure 7.3) (Liu et al., 2004). It was revealed that each 25kDa protein monomer contains three transmembrane and three amphiphilic a-helixes. In addition, each monomer binds 14 chlorophyll (8 Chi a and 6 Chi b) and 4 xanthophyll molecules 1 neoxanthin, 2 luteins, and 1 violaxanthin. The first three xanthophylls are situated close to the integral helixes and are tightly bound to some amino acids by hydrogen bonds to hydroxyl oxygen atoms and van der Waals interactions to chlorophylls, and hydrophobic amino acids such as tryptophan and phenylalanine. 

A typical virus with helical symmetry is the tobacco mosaic virus (TMV). This is an RNA virus in which the 2130 identical protein subunits (each 158 amino acids in length) are arranged in a helix. In TMV, the helix has 16 1/2 subunits per turn and the overall dimensions of the virus particle are 18 X 300 nm. The lengths of helical viruses are determined by the length of the nucleic acid, but the width of the helical virus particle is determined by the size and packing of the protein subunits. 

Since the primary structure of a peptide determines the global fold of any protein, the amino acid sequence of a heme protein not only provides the ligands, but also establishes the heme environmental factors such as solvent and ion accessibility and local dielectric. The prevalent secondary structure element found in heme protein architectures is the a-helix however, it should be noted that p-sheet heme proteins are also known, such as the nitrophorin from Rhodnius prolixus (71) and flavocytochrome cellobiose dehydrogenase from Phanerochaete chrys-osporium (72). However, for the purpose of this review, we focus on the structures of cytochromes 6562 (73) and c (74) shown in Fig. 2, which are four-a-helix bundle protein architectures and lend themselves as resource structures for the development of de novo designs. 

Wierenga RK, De Maeyer MC, Hoi WGJ. Interaction of pyrophosphate moieties with a-helixes in dinucleotide binding proteins. Biochemistry 24 1985 1346-1357. 

The structure of IFN-x was also examined by CD [10]. Analysis of the IFN-x spectra predicts that the secondary structural elements derived from CD spectra indicate approximately 70% a-helix. The remainder of the molecule is either predicted to be random or a combination of (3 sheet and turn. Since it is known that algorithms that predict secondary structures from CD spectra are most accurate at identifying a helices, we are confident that IFN-x is mainly a helical. The CD spectra for the synthetic peptides of IFN-x were also obtained. The peptides IFN-x(l-37), IFN-x(62-92), IFN-x(l 19-150), and IFN-x(139-172) all show the presence of a helix, while IFN-x(34-64) and IFN-x(90-122) are mainly random. The presence of an a helix in the peptides supports the CD analysis of the intact protein and also roughly indicates the location of helical segments. 

The usefulness of infrared spectroscopy of proteins and membranes is increased when spectra of dry films are compared with those taken in deuterium oxide. Exchange of protons for deuterons can affect both the amide I and amide II bands. For randomly coiled proteins in D20 the amide I band is shifted down by about 10 cm."1 but for many proteins D20 does not affect the frequency of the carbonyl stretch of either the ft structure or the a-helix. In addition, upon complete exchange the amide... 

---