Heptads

C19H40S ETHYL-HEPTADE- CYL-SULFIDE -382.174 1.6836E+00 2.3903E-04 141.29... 

Coiled-coil a helices contain a repetitive heptad amino acid sequence pattern... 

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.

In the heptad sequence ate close to the hydrophobic core and can form salt bridges between the two a helices of a colled-coll structure, the e-resldue In one helix with the g-resldue In the second and vice versa. 

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. 

Helices widi a heptad repeat of hydrophobic residues... 

It is usual to discuss triads, tetrads, pentads, etc. in terms of the component dyads. For example, the mrrrmr heptad is represented as shown in Figure 4.3. 

Figure 4.3 Representation of mrrrmr heptad identifying component u-ads.

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... 

Xu L, Pozniak A, Wildfire A, Stanfield-Oakley SA, Mosier SM, RatcUffe D, Workman J, JoaU A, Myers R, Smit E, Cane PA, Greenberg ML, Pillay D (2005) Emergence and evolution of enfu-virtide resistance following long-term therapy involves heptad repeat 2 mutations within gp4L Antimicrob Agents Chemother 49 1113-1119... 

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)... 

---