Coiled-coil motif/structure

Despite their lack of stabilizing disulfide bridges Potl inhibitors feature a common, stable fold. The N-terminus is coiled, although in some structures a small /3-strand has been identified. After a turn the structure adopts an a-helical structure, followed by a turn and an other /3-strand. The sequence then features an extended turn or loop motif that contains the reactive site of the inhibitor before it proceeds with a /3-strand running almost parallel to the /3-strand after the a-helix. After another turn and coiled motif a short /3-strand antiparallel to the other /3-strands precedes the coiled C-terminus. Usually the N-terminal residue in the reactive site is an acidic residue followed by an aromatic amino acid, that is, tyrosine or phenylalanine. Figure 11 shows the complex of chymotrypsin inhibitor (Cl) 2 with subtilisin, the hexamer of Cl 2 from H. vulgare and a structural comparison with a trypsin inhibitor from Linum usitatissimum ... 

The coiled-coil motif is not strictly a specific fold but the description is appHed to structures where helical segments are based on the heptad repeat abcdefg) . 

By examining the amino add sequence of tropomyosin, the smallest and simplest proteins postulated at the time 1819 to contain the coiled-coil motif, we identified the hydrophobic repeat responsible for the formation and stabilization of the coiled-coil structure. 18 A coiled coil can be considered as a repeating heptad of seven amino acid residues a-b-c-d-e-f-g, where positions a and d are occupied by hydrophobic residues. This 3-4 (or 4-3) hydro-... 

The coiled-coil motif is an ideal model system for the following reasons there is only one type of secondary structure present (the a-helix) the a-helical structure can be easily monitored by circular dichroism spectroscopy the two-stranded coiled coil contains two subunits stabilized by both intrachain and interchain interactions and, lastly, its small size reduces the potential complexity in the analysis and interpretation of results encountered in the analysis of globular proteins, which have multiple elements of secondary structure (a-helix, (3-sheet, (3-turns, loops, and regions of undefined structure). 

Walshaw, J., and Woolfson, D. N. (2001). SOCKET A program for identifying and analyzing coiled-coil motifs within protein structures. J. Mol. Biol. 307, 1427-1450. 

In addition to the alpha, beta, and random coil motifs in the secondary structure of protein depicted... 

Coiled coil, motifs of super-secondary structure found in proteins. Approximately 2-3% of aU proteins form coiled coils, where two to seven amphipathic a-helices are wrapped around each other, like the strands of a rope. The interaction surface of these amphipathic helices is of hydrophobic nature, and leucine is often found in the position of the hydrophobic amino acids (leucine zipper). This hydrophobic interaction provides, in an aqueous environment, the driving force for the di- or oligomerization. Coiled coils of two or three helical domains are the most commonly found types. In the former case, the two helices are wound up against each other in a left-handed twist with a seven-residue periodicity. Packing of unpolar side chains (u) into a hydrophobic core mainly contributes to the stability of this super-secondary fold. The dimeric coiled coU is, for example, responsible for DNA recognition by some transcription factors. 

Figure 22 Schematic illustration of the peptide-guided organization of peptide-polymer conjugates by the self-assembly of peptide-aggregator domains. Peptide structure motifs such as p-sheet and a-helical coiled-coil (left) and peptide-guided organization of bioconjugates (right) forming fibrillar structures by the p-sheet secondary structure and distinct nano-objects by the coiled-coil motif (bottom).

Well-defined nano-objects could be realized by the groups ofVandermeulen etal. and Pecharetal. independently, exploiting the coiled-coil motif to control the formation of distinct a-helical bundles. The coiled-coil structure motif is char-... 

Beyond artificial tertiary folds are quaternary structures for which natural coiled-coil motifs represent an important source of inspiration. A representative coiled-coil is GCN4—a yeast transcription regulator protein containing... 

Inspired by a-helices in nature and their ability to self-assemble into oligomeric coiled coils, a number of researchers have tailored helical peptides in order to generate fibrous structures. As an example, Woolfson and coworkers ° described the design of a single-peptide, based on an a-helical coiled-coil motif, named MagicWand, which self-assembled into extended and thickened nano-to mesoscale fibers of high stability and order. The peptide had a heptad sequence repeat, abcdefg, with isoleucine and leucine residues at the a and d sites to promote dimerization. 

Fluorinated amino acids have been incorporated into the hydrophobic cores of coiled coils in order to modulate physical and biological properties of the ensembles and quantify resulting changes in conformational stability. Coiled-coil motifs, wherein two or more helical peptide strands interact to form higher order structures, are ubiquitous in nature and have been well studied. They contain a typical heptad repeat sequence (abcdefg) in which positions a and d make up the hydrophobic core and charged residues at positions e and g interact electrostatically. Amino acids in coiled-coil... 

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