Helical Folds

These results indicate that is it possible to change the fold of a protein by changing a restricted set of residues. They also confirm the validity of the rules for stability of helical folds that have been obtained by analysis of experimentally determined protein structures. One obvious impliction of this work is that it might be possible, by just changing a few residues in Janus, to design a mutant that flip-flops between a helical and p sheet structures. Such a polypeptide would be a very interesting model system for prions and other amyloid proteins. 

Fig. 2.3 Model of the 2i- and 3i-helical structures proposed for PHB chains with ideal torsion angle values. The 2i-helix was determined by fiber X-ray diffraction of PHB [49-51] while the 3i-helical fold was constructed by using preferred dihedral angles found along the backbone in crystal structures of cyclic oligomers 9 ( oligolides ) [37, 43, 45]...

These studies conducted in solution and in the solid state revealed a common 3i4-helical fold stabilized by H-bonds closing 14-membered rings formed between NH and C=0 +2 (see Fig. 2.12A and C). It is noteworthy that the 3i4-helix of j -peptides with L-amino acid-derived chirality centers (Fig. 2.12 A) and the a-helix have opposite polarity and helicity. 

HAIa) distributed in a complementary manner on one face of the 3,4-helix. Charged side-chains are included to stabilize the helical fold in aqueous solution. Reprinted with permission from [179], American Chemical Society (2002)... 

Fig. 2.36 The y-peptide 2.614-helical fold. (A) Stereo-view along the helix axis of the (P)-2.6i4-helical structure adopted by y -hexapep-tide 141 in pyridine. This low energy confor-mer was obtained by simulated annealing calculations under NMR restraints. Side-chains have been partially omitted for clarity.

Interestingly, 8-aminoxy acids which are homologs of y-amino acids have also been found to promote the formation of turns and helices. In apolar solvent and in the solid state, model diamides consisting of /9 -aminoxy add residues adopt a novel N-O turn stabilized by both a nine-membered H-bonded ring between C=0 and NHj+2, and a six-membered ring formed between N-O and NH +1. The X-ray crystal structure of a corresponding triamide revealed two consecutive C9 N-O turns suggesting a novel 1.79-helical fold [279]. 

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. 

E. Boy de la Tour, and U. K. Laemmli, The metaphase scaffold is helically folded Sister chromatids have predominantly opposite helical handedness. Cell 55, 937-944 (1988). 

Short peptides three to five residues in length that contain one or two APhe residues adopt a fJ-bend 45"48 and 310-helical folding. For example, crystal structure studies of a three-residue peptide containing two APhe residues, Ac-APhe-Ala-APhe-NHMe, 49 and a five-residue peptide with one APhe residue, Boc-Leu-Phe-Ala-APhe-Leu-OMe, 50 show the presence of two consecutive (3-bends, corresponding to an incipient 310-helix in both peptides. Such didehydropeptides exist in both screw senses and the spacing between APhe residues does not seem to affect the type of helix formed. 51,52 ... 

Fig. 12. Templating a-helices using compound 25 [24b], The template (bottom part) serves to initiate the helical folding by forming the first hydrogen bonds. (Reproduced with the permission of Ref. 24b)...

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...

Fig. 4. Thermodynamic models of membrane protein folding. (A) In the two-step model of folding, the TM helices fold and insert into the membrane and subsequently move laterally to associate (Popot and Engelman, 1990). (B) White and co-workers constructed an expanded model, which includes the protein residing in water (states 1-3), the interfacial region (states 4 and 5), and the membrane core (states 6 and 7) (White and Wimley, 1999).

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