Coiled-coils

A single helix is a coil a double helix is two nested coils The tertiary structure of DNA in a nucleosome is a coiled coil Coiled coils are referred to as supercoils and are quite common... 

While PEO was a semi-crystalline polymer, it behaved essentially as random coils in a solvated state in water. Thus, the Eisenberg system fell under the category of coil-coil diblock copolymers. Another example of this category was nanotube formation from a family of coil-coil-coil ABA triblock copolymers poly(2-methyloxazoline)-foiocfc-poly(dimethylsdoxane)-foiocfc-poly(2-methyloxazoline)or PMOXA-PDMS-PMOXA, where the PMOXA blocks were water soluble. 

Aside from the coil-coil diblocks and coil-coil-coil ABA triblocks, crystalline-coU poly(ferrocenyldimethylsilane)-foZock-poly(dimethyl silox-ane) or PFS-PDMS diblock copolymers were reported by Raez, Manners, and Winnik [42] to form nanotubes readily in block-selective solvents hexane and n-decane, which solubilized the rubbery PDMS blocks and not the crystalline PFS blocks. 

Block copolymer nanotubes can be prepared either directly from block copolymer self-assembly in block-selective solvents or from the chemical processing of ABC triblock copolymer nanofibers. There has been only one report on the formation of self-assembled nanotubes from coil-coil AB diblocks in block selective solvents, and it occurred for a sample with a very low weight fraction of the soluble block. Nanotubes were formed from coil-coil-coil ABA triblock copolymers at much higher weight fractions for the soluble A blocks. Still, lower soluble block weight fractions were required for nanotube than for vesicle formation. It remains to be seen if these trends can be generalized to other block copolymers containing purely coil blocks. 

OgjharaNL, Weiss MS, Degrade WF,Eisenberg D (1997) The crystal structure of the designed trimeric coiled coil coil-VaDi Implications for engineering crystals and supramolecular assemblies. Protein Sci 6 80-88... 

Substance inside coil Substance outside coil Coil material Agitation V... 

Tvpe of coil Coil spacing, in.f Fluid in coil Fluid in vessel Temp, range, F. without cement if with heat-transfer cement... 

WA Lim, A Hodel, RT Sauer, FM Richards. The crystal structure of a mutant protein with altered but improved hydrophobic core packing. Proc Natl Acad Sci USA 91 423-427, 1994. PB Harbury, B Tidor, PS Kim. Repacking proteins cores with backbone freedom Structure prediction for coiled coils. Pi oc Natl Acad Sci USA 92 8408-8412, 1995. 

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

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

Figure 3.2 Repetitive pattern of amino acids in a coiled-coil a helix.

Detailed structure determinations of GCN4 and other coiled-coil proteins have shown that the a helices pack against each other according to the "knobs in holes" model first suggested by Francis Crick (Figure 3.5). Each side chain in the hydrophobic region of one of the a helices can contact four side chains from the second a helix. The side chain of a residue in position "d"... 

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.

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

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.

Cohen, C., Parry, D.A.D. Alpha-helical coiled coils—a widespread motif in proteins. Trends Biochem. Sci. 

Crick, F.H.C. The packing of a-helices simple coiled coils. Acta Cryst. 6 689-697, 1953. 

Residues 50-64 of the GAL4 fragment fold into an amphipathic a helix and the dimer interface is formed by the packing of these helices into a coiled coil, like those found in fibrous proteins (Chapters 3 and 14) and also in the leucine zipper families of transcription factors to be described later. The fragment of GAL4 comprising only residues 1-65 does not dimerize in the absence of DNA, but the intact GAL4 molecule does, because in the complete molecule residues between 65 and iOO also contribute to dimer interactions. 

Subsequently Stephen Harrison s group determined the x-ray structure of a PPRl-DNA complex and showed that the zinc cluster domain of PPRl and its mode of binding to DNA was very similar to that of GAL4, and that PPRl also dimerized through a coiled-coil region. However, the linker region... 

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... 

Figure 10.28 Schematic diagram of the binding of the transcription factor Max to DNA. The two monomers of Max (blue and green) form a dimer through both the helix-loop-helLx regions which form a four-helix bundle like MyoD, and the zipper regions, which are arranged in a coiled coil. The N-terminal basic regions bind to DNA in a way similar to GCN4 and MyoD. (Adapted from A.R. Ferre-D Amare et al., Nature 363 38-4S, 1993.)...

Dimerization of the Ce-zinc cluster transcription factors involves an a-helical coiled coil in the dimerization region. Coiled coils, often called leucine zippers, are also found in a large group of transcription factors that do not contain zinc. The leucine zipper is made up of two a helices in a coiled coil with every seventh residue leucine or some other large hydrophobic residue, such as isoleucine or valine. Leucine zipper transcription factors (b/zip) include factors characterized by heterodimerization, for example Fos and Jun. The a-helical DNA-binding motifs of the heterodimers recognize quite different base sequences and are continous with the a helices of the zipper. 

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