Heptad in coiled coil

As long ago as 1984, Lau et al.1311 demonstrated that stable coiled coils of four heptads in length could be formed. Subsequent work set out to examine the factors that would maximize stability of the coiled coil in the shortest possible chain length, for example, hydro-phobicity and packing effects in the hydrophobic core, intrachain electrostatic interactions, and the helical propensity contribution of residues outside the hydrophobic interface.123,24 30 321... 

Fig. 1. Gallery of canonical, heptad-based coiled-coil proteins. Coiled-coil segments are shown in red, other a-helices in yellow, and /3-strands in green.

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... 

Figure 3.3 Schematic diagram showing the packing of hydrophobic side chains between the two a helices in a coiled-coil structure. Every seventh residue in both a helices is a leucine, labeled "d." Due to the heptad repeat, the d-residues pack against each other along the coiled-coil. Residues labeled "a" are also usually hydrophobic and participate in forming the hydrophobic core along the coiled-coil.

We described in Chapter 3 the basic features of a-helical coiled coils whose amino acid sequences are recognized by heptad repeats a to in which positions a and d frequently are hydrophobic residues (see Figures 3.2 and 3.3). 

The leucine zipper DNA-binding proteins, described in Chapter 10, are examples of globular proteins that use coiled coils to form both homo- and heterodimers. A variety of fibrous proteins also have heptad repeats in their sequences and use coiled coils to form oligomers, mainly dimers and trimers. Among these are myosin, fibrinogen, actin cross-linking proteins such as spectrin and dystrophin as well as the intermediate filament proteins keratin, vimentin, desmin, and neurofilament proteins. 

The coiled-coil fibrous proteins have heptad repeats in their amino acid sequence and form oligomers—usually dimers or trimers—through their coiled coils. These oligomeric units then assemble into fibers. 

Many enveloped viruses share a common mechanism of fusion, mediated by a virus-encoded glycoprotein that contains heptad repeats in its extraceUnlar domain. Dnring the fnsion process, these domains rearrange to form highly structured and thermodynamically stable coiled-coils. Viruses encoding fusion proteins that have these domains inclnde members of the paramyxovirus family (e.g., respiratory syncytial virus, metapneumovirus, and measles virus), ebola virus, influenza, and members of the retroviridae (e.g., human T cell lenkemia virus type-1 and human immunodeficiency virus type-1, HlV-1). Peptide inhibitors of fusion that disrupt the... 

The characteristic coiled-coil motifs found in proteins share an (abcdefg) heptad repeat of polar and nonpolar amino acid residues (Fig. 1). In this motif, positions a, d, e, and g are responsible for directing the dimer interface, whereas positions b, c, and f are exposed on the surfaces of coiled-coil assemblies. Positions a and d are usually occupied by hydrophobic residues responsible for interhelical hydrophobic interactions. Tailoring positions a, d, e, and g facilitates responsiveness to environmental conditions. Two or more a-helix peptides can self-assemble with one another and exclude hydrophobic regions from the aqueous environment [74]. Seven-helix coiled-coil geometries have also been demonstrated [75]. 

Fig. 1 (a) Side and (b) top view of a parallel two-stranded coiled-coil based on heptad sequence repeat (abcdefg). Residues at positions a, d, e and g form the interface between a-helices in a coiled coil stmcture. Prime notations are used to distinguish analogous positions in the two helices fOT example, a and d are analogous positions. Reproduced from Fong et al. [73] licensee BioMed Central Ltd. copyright 2004 (http //genomebiology.eom/2004/5/2/Rll)... 

The staggered pattern, unlike the design in the SAF peptides modulated by the side chain interaction, was created because of the identical heptad repeats along the entire peptide that tends to form offsets within the multistranded coiled coil assembly. The resultant stmcture with overhanging ends presents the hydrophobic amino... 

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