The Alacoil:
A very tight, antiparallel coiled-coil of helices 		        
    
    
        The Alacoil is an antiparallel (rather than the usual parallel) coiled-coil of alpha-helices with Ala or another small residue in every seventh position. It puts the two helices significantly closer together(7.5A-8.5A) than any previously described type of coiled-coil, and yet it is fairly common, with long examples so far identified in several unrelated proteins. It occurs in two distinct types that differ by which position of the heptad repeat is occupied by Ala and by whether the closest points on the backbone of the two helices are aligned or are offset by half a turn. The aligned, or ROP, type has Ala in position "d" of the heptad repeat, which occupies the "tip-to-tip" side of the helix contact where the Calpha-Cbeta bonds point toward each other. The more common offset, or ferritin, type of Alacoil has Ala in position "a" of the heptad repeat (where the Calpha-Cbeta bonds lie back-to-back, on the "knuckle-touch" side of the helix contact), and the backbones of the two helices are offset vertically by half a turn. In both forms, successive layers of contact have the Ala first on one and then on the other helix.In addition to the hydrophobicity of Ala, other hydrophobic side chains on an outer face of the Alacoil take part in some interactions(e.g. salt link) to stable the Alacoil structure.

The Alacoil structure has much in common with the coiled-coils of fibrous proteins or leucine zippers: both are alpha-helical coiled-coils, with a critical amino acid repeated every seven residues (the Leu or the Ala) and a secondary contact position in between. However, Leu zippers are between aligned, parallel helices (often identical, in dimers), whereas Alacoils are between antiparallel helices, usually offset, and much closer together. The Alacoil, then, could be considered as an "Ala anti-zipper." Leu zippers have a classic "knobs-into-holes" packing of the Leu side chain into a diamond of four residues on the opposite helix; for Alacoils, the helices are so close together that the Ala methyl group must choose one side of the diamond and pack inside a triangle of residues on the other helix.

Beacause the achieving of unique, well-ordered structure and the possible tradeoffs between stability and uniqueness are currently central issues in the field of de novo protein design, experimental exploration of the properties of Alacoils could make a useful contribution. We have used the ferritin-type Alacoil as the basis for the de novo design of a 66-residue, coiled helix hairpin called"Alacoilin." Its sequence is: cmSPDQWDKE AAQYDAHAQE FEKKSHRNng TPEADQYRHM ASQYQAMAQK LKAIANQLKK Gsetcr (with "a" heptad positions underlined and nonhelical parts in lowercase), which we will produce and test for both stability and uniqueness of structure.

    
         
       
    
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