Coiled Coil Domains: Stability, Specificity, and Biological Implications

TL;DR: The importance of individual amino acids in maintaining -helical structure (intramolecular interactions) within individual helices, whilst promoting specific coiled-coil interactions (intermolecular interaction) of correct oligomeric state and orientation is outlined.

Abstract: The coiled coil is a common structural motif, formed by approximately 3 ± 5% of all amino acids in proteins. Typically, it consists of two to five -helices wrapped around each other into a left-handed helix to form a supercoil. Whereas regular -helices go through 3.6 residues for each complete turn of the helix, the distortion imposed upon each helix within a left-handed coiled coil lowers this value to around 3.5. Thus a heptad repeat occurs every two turns of the helix. 3] The coiled coil was first described by Crick in 1953. He noted that -helices pack together 20 away from parallel whilst wrapping around each other, with their side chains packing TMin a knobs-into-holes manner∫. The same year, Pauling and Corey put forward a model for -keratin. It was some 20 years later that the sequence of rabbit skeletal tropomyosin was published, and another twenty until the first structure of the leucine zipper motif was solved by Alber and co-workers. These last discoveries pushed the coiled-coil field into the spotlight, as it became apparent that they are found in important structures that are involved in crucial interactions such as transcriptional control. The most commonly observed type of coiled coil is left-handed; here each helix has a periodicity of seven (a heptad repeat), with anywhere from two (in designed coiled coils) to 200 of these repeats in a protein. This repeat is usually denoted (a-b-c-d-e-fg)n in one helix, and (a -b -c -d -e -f -g )n in the other (Figure 1). In this model, a and d are typically nonpolar core residues found at the interface of the two helices, whereas e and g are solventexposed, polar residues that give specificity between the two helices through electrostatic interactions. Similarly in righthanded coiled coils, an eleven-residue repeat is observed (undecatad repeat). 11] The apparent simplicity of the structure with its heptad periodicity has led to extensive studies. Here we aim to outline the importance of individual amino acids in maintaining -helical structure (intramolecular interactions) within individual helices, whilst promoting specific coiled-coil interactions (intermolecular interactions) of correct oligomeric state and orientation. The PV Hypothesis