Coiled coils structures

Figure 3.1 Schematic diagram of the coiled-coil structure. Two a helices are intertwined and gradually coil around each other.

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.

Figure 3.S Schematic diagram of packing side chains In the hydrophobic core of colled-coll structures according to the "knobs In holes" model. The positions of the side chains along the surface of the cylindrical a helix Is pro-jected onto a plane parallel with the heUcal axis for both a helices of the coiled-coil. (a) Projected positions of side chains in helix 1. (b) Projected positions of side chains in helix 2. (c) Superposition of (a) and (b) using the relative orientation of the helices In the coiled-coil structure. The side-chain positions of the first helix, the "knobs," superimpose between the side-chain positions In the second helix, the "holes." The green shading outlines a d-resldue (leucine) from helix 1 surrounded by four side chains from helix 2, and the brown shading outlines an a-resldue (usually hydrophobic) from helix 1 surrounded by four side chains from helix 2.

Figure 3.8 Schematic diagram of the dimeric Rop molecule. Each subunit comprises two a helices arranged in a coiled-coil structure with side chains packed into the hydrophobic core according to the "knobs in holes" model. The two subunits are arranged in such a way that a bundle of four a helices is formed.

The coiled-coil structure of the leucine zipper motif is not the only way that homodimers and heterodimers of transcription factors are formed. As we saw in Chapter 3 when discussing the RNA-binding protein ROP, the formation of a four-helix bundle structure is also a way to achieve dimerization, and the helix-loop-helix (HLH) family of transcription factors dimerize in this manner. In these proteins, the helix-loop-helix region is preceded by a sequence of basic amino acids that provide the DNA-binding site (Figure 10.23), and... 

Hydrogels Based on a-Helical Coiled-Coil Structures... 

Our strategy for the spontaneous dimerization of EGF was to incorporate an ot-helical oligopeptide with the ability to participate in forming a coiled-coil structure [99]. We implemented a heterodimerization system in which (KELASVK)5 (K5) and (EKLASVE)5 (E5) peptides could form stable coiled-coil heterodimers. We then synthesized two chimeric proteins that contained EGF attached to either the K5 (EGF-K5-His) or the E5 (EGF-E5-His). Both had the hexahistidine sequence added to the C-terminus for anchoring through coordination with Ni2+ ions fixed to a substrate. 

A number of research groups have taken up this challenge and have developed rationally designed peptides adopting coiled coil structures that self-assemble into more complex nanostmctures. As a dominating and perhaps the most practical form of nanostructures, nanofiber assembly serves to illustrate the hierarchical molecular self-assembly possible in these systems. 

The original system is based on peptides that contain heptad repeats, where the first and fourth positions of the repeat are hydrophobic amino acids. Such sequences form a-helices, which assemble into coiled-coil structures, as represented in Figure 7.10. The principle is then the same as that used for von Kiedrowski s self-replicating nucleotides (von Kiedrowski 1986), in the sense that a full-length peptide template (having in this case 32-35 residues) directs the condensation of the two half-length peptide substrates. 

Figure 7.10 Coiled-coil structures during peptide condensation, (a) Two peptides containing heptad repeats (A to F and A to F ) able to form a-helices. Hydrophobic interactions (A-A and D-D ) lead to coiled-coil structures, (b) A full-length peptide (T) acts as a template forming a coiled-coil structure with peptide fragments and directing their condensation in other full-length peptides (B). (Adapted from (a) Paul and Joyce, 2004 (b) Ghosh and Chmielewsld, 2004.)...

Coiled coils. In a large family of proteins, two right-handed a helices are coiled around each other in a left-handed superhelix (Fig. 2-21).161-167 This coiled coil structure was first suggested by Francis Crick166... 

Each of the monomeric proteins c-jun and c-fos, as well as other members of the leucine zipper family, has an N-terminal DNA-binding domain rich in positively charged basic amino acid side chains, an activation domain that can interact with other proteins in the initiation complex, and the leucine-rich dimerization domain.363 The parallel coiled-coil structure (Fig. 2-21) allows for formation of either homodimers or heterodimers. However, cFos alone does not bind to DNA significantly and the cjun/cFos heterodimer binds much more tightly than does cjun alone.364 The yeast transcriptional activator protein GCN4 binds to the same 5 -TGACTCA sequence as does the mammalian AP-1 and also has a leucine zipper structure.360 364 365... 

An illustration of the coiled-coil structure of the nucleosome is presented in figure 25.18. The 140 bp of DNA... 

H3, and H4, is packed on the inside of the DNA coiled-coil structure. ( Scientific American, Inc., George V. Kelvin. Reprinted with permission.)... 

In the chromatin of eukaryotic cells DNA forms a coiled-coil structure with an approximately equal weight of a mixture of five basic proteins known as histones. Four of these histones in pairs form an octa-mer around which the DNA duplex occurs in a left-handed helix. The DNA octamer complex is called a nucleosome. Each nucleosome contains about 140 base pairs of DNA in a nuclease-resistant nucleosome core and approximately 60 base pairs of spacer between core particles. Histone HI binds to the chromatin independently of the octamer and is the first histone to dissociate from the chromatin when the ionic strength is raised. Beyond the nucleosome the higher order structure of the chromosome involves coiled-coil structures with varying degrees of regularity. 

CD) in comparison with the star shaped analog 43. They also showed that 42 is incorporated easily into phospholipid bilayers. On the other hand, the same group reported the preparation of the coiled coil structure 44 with two amphiphilic 14-residue peptides linked to a bipyridyl template [37], The incorporation of a fluorescent probe, pyrenyl-L-alanine, near the supercoiling region helped them to demonstrate by fluorescence the formation of the proposed structure in water. 

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-... 

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