A-helical folds

The three-dimensional structure of NPY when bound to the membrane is shown in Fig. 5.6. It comprises an a-helix for residues 16 to 36 which is very well defined, and a flexible N-terminal part of the molecule. When comparing the structure of the DPC-mi-celle bound form to the structure in free solution, it is obvious that the a-helix is much more stable. In addition, the C-terminus of the helix comprising residues 32-36, which is flexible in solution, adopts an a-helical fold, and the Tyr36 is oriented such that it interacts with the water-membrane interface. 

Reversible chemical oxidation reactions have also been used to control and modulate the conformation of polypeptide chains.119,101 By converting methionine to its sulfoxide, Gellman and co-workers were able to control the secondary structure of an 18-residue peptide. The side chain of a methionine residue (containing a CH2CH2SCH3 fragment) is hydrophobic and favors a-helical folding. Oxidation to the methionine sulfoxide state results in a preference for a (i-strand situation. 

The developmental patterns and structures of CSPs and OBPs are also different. The CSPs are produced synchronously to the shedding of the cuticle, very early during adult development, in contrast to OBPs which are produced late during adult development. This demonstrates that the chemosensory CSPs and olfactory OBPs are controlled by independent mechanisms (Vogt et al., 1993 Picimbon et al., 2001 Gavillet and Picimbon, 2002). Moreover, X-ray structure analysis of CSPs has revealed a novel type of a-helical fold with six helices connected... 

Component Selection on Formation of a Helically Folded Molecular Strand... 

Fig. 14 Component recombination under selection induced by formation of a helically folded molecular strand...

At the present time, representative stmctures exist for approximately 21 unique P-barrel membrane protein families and 35 polytopic a-helical protein families. This sample is a small fraction of the predicted 300-500 a-helical folds and 700-1700 families (3). Although the stmctural biology of membrane proteins is in its infancy, it is clear that membrane proteins display a rich variety of structures that vary greatly in size and topology (Fig. 1). Of the structures observed thus far, all are based on two fundamental architectures the a-helical bundle (4) and the 3-barrel (5, 6). 

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... 

The a helix contains a helical folding of the polypeptide backbone such that a hydrogen bond is formed between the carbonyl group of residue i and the amide nitrogen atom of residue i+4. 

Ideal a helices fold on to ideal p sheets with their axes parallel to the strands. Some small ot/p proteins contain just two layers, i.e. a helices packed on one side of a P sheet. However, the large majority of proteins have three layer structures with a helices packed on both sides of a P sheet. In the ot/p barrel, a P sheet coils round to form a closed cyUn-der. The barrel stractures are formed by eight parallel strands of P sheets, which are linked by a helices with their axes approximately parallel to the strand direction. 

Figure 8.1 Tertiary structure. P-pleated sheets and a-helices fold themselves to form two different creatine kinase (CK) monomers (CK-M and CK-B).

Fig. 11 Adaptation of the set of multifunctional dynamers PI, P2, P3, and P4 (see Fig. 10) by variation in constitutional distribution in response to the addition of alkali metal cations Li, Na, K, Rb, and Cs. The initial relative amounts of the four dynamers are shown in pale colors (on the left of each set). Large variations in relative amounts are obstaved on addition of alkali metal cations. A marked increase in the fraction of the trifunctional dynamer P3, containing the donor, acceptor, and cation binding fragments, occurs as a result of its ability to bind alkali cations in a helically folded form (shown in the top middle). The fraction of its agonist P4 is increased similarly, whereas the fractions of antagonists PI and P2 are strongly decreased. The changes occurring in the case of Na are shown in darker colors. Pld. P2d. P3d, and P4d indicate the repeat units of the four corresponding dynamers...

FIGURE 8.5 Structuration of an IDP upon binding to membrane lipids. When an IDP comes close to a membrane, specific interactions with selected lipids (such as gangliosides in lipid rafts) will favor the efficient adhesion of the protein to this membrane. Moreover, the repetitive head groups of raft lipids wiU induce a-helical folding of the protein through a typical chaperone-facilitated reaction. The reduction of dimensionality from 3D (extracellular milieu) to 2D (hpid raft surface) also favors the concentration of the protein on the membrane surface. The Parkinson s and Alzheimer s disease-associated proteins a-synuclein and p-amyloid peptides (Ap) are typical examples of such IDPs that acquire a helical structure when bound to hpid rafts of neural cells. 

Bartels T, Choi JG, SeUcoe DJ. Alpha-s)mudein occurs physiologically as a helically folded tetramer that resists aggregation. Nature. 2011 477(7362) 107-110. 

Tashiro S, Tominaga M, Yamaguchi Y, Kato K, Fujita M (2006) Peptide recognition encapsulation and a-helical folding of a nine-residue peptide within a hydrophobic dimeric capsule of a bowlshaped host. Chem Eur J 12 3211-3217... 

Fig. 9.2 a Helically folded pyridine-based oligomer 4, b alternative conformations 5a and 5b versus 4, c helically folded methoxybenzene-based foldamers 6a and d pyridine-based foldamers 6b that assemble into a double stranded structure... 

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