Coiled coils may be used in the design of self-assembling macro-molecular structures. To form such a structure, it is necessary that each molecule interacts with at least two others, which in turn interact with other molecules. There are two ways in which this may be achieved using the coiled-coil system and these are illustrated below in the context of parallel dimeric coiled coils.
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Firstly, each helix may have two (or more) distinct sections, which interact with different helices. This strategy has been successfully used by the group to produce self-assembling fibres. An alternative method for self-assembly is for each helix to have two (or more) faces formed by overlaying two (or more) heptad repeats as described below.
Few natural examples exist of these multi-faceted helices. Most are short and antiparallel. One of the best examples of the simplest structure, the three-helix sheet, is in the transactivation domain of protein E2 from human papilloma virus. This is shown below.
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These structures are formed by overlaying two heptad repeats, so that the c & f residues (in addition to the a & d residues) act as knobs. It is not possible (while retaining a supercoil) to have the two stripes immediately opposite each other, and therefore there will be an angle between any three helices in a sheet. By putting helices together in different ways, it is possible to either make these angles cancel out, forming extended alpha-sheets, or to reinforce each other, leading to alpha-cylinders. This latter strategy is the assembly method used by the bacterial export protein Tol-C (below) to form the only known example of an alpha-cylinder. All the helices in the barrel are anti-parallel. (Koronakis et al., Nature 405, 2000).
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We believe that it should be possible to utilise these types of interaction in the design of self-assembling sheets and nanotubes. For more detailed discussion on this subject, see J Walshaw & DN Woolfson, Protein Science 10: 668-673 2001.