The coiled coil is a ubiquitous protein motif that is often used to control oligomerisation. It is found in many types of proteins, including transcription factors (eg: GCN4, shown below), viral fusion peptides, SNARE complexes and certain tRNA synthetases. Very long coiled coils are found in proteins such as tropomyosin, intermediate filaments and spindle-pole-body components.
Coiled coils are ideal candidates for protein folding and design studies, as they represent probably the simplest tertiary structure. They involve a number of alpha-helices wound around each other in a highly organised manner, similar to the strands of a rope. There may be between two and five helices in the structure, although dimers and trimers are the most common. The helices may be from the same or from different proteins.
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Most coiled-coil sequences contain heptad repeats - seven residue patterns denoted abcdefg in which the a and d residues (core positions) are generally hydrophobic. As there are 3.6 residues to each turn of the alpha-helix, these a and d residues form a hydrophobic seam (seen in red below), which, as each heptad is slightly under two turns, slowly twists around the helix.
The coiled-coil is formed by component helices coming together to bury their hydrophobic seams. As the hydrophobic seams twist around each helix, so the helices also twist to coil around each other, burying the hydrophobic seams and forming a supercoil. It is the characteristic interdigitation of side chains between neighbouring helices, known as knobs-into-holes packing, that defines the structure as a coiled coil (Crick, 1953).
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The helices do not have to run in the same direction for this type of interaction to occur, although parallel conformation is more common. Antiparallel conformation is very rare in trimers and unknown in pentamers, but more common in intramolecular dimers, where the two helices are often connected by a short loop.
Although this heptad arrangement is most prevalent, alternative packing strategies also exist. Hendecad repeats (11 residues)
are found in long filamentous proteins, and such alternative repeat-patterns may contribute to partner choice (Hicks et al.,
1997. Abstract).
We study coiled-coil motifs by analysing known structures and by developing new theories for coiled-coil folding and assembly. SOCKET, a program that unambiguously identifies knobs-into-holes packing is available for use over the web or may be downloaded. A database containing details of structures identified by SOCKET from the PDB is also available for public use. These are contained within the Hard-boiled Coiled Coils resource.
The rules that are gleaned from these studies are used to design and construct novel coiled-coil peptides and self-assembling systems.
The group is also involved in improving prediction of coiled coils from sequence. The following external web resources are presently available for this purpose:
Coils
Paircoil at MIT
Multicoil at MIT
Further Links - including where to get the above software:
Prediction of Coiled Coils from Protein Sequences
at the University of York
References
Hicks MR et al., Folding & Design 2(3) 149-158 (1997) Abstract