Computer modelling of the alpha-helical coiled coil: packing of side-chains in the inner core.
In order to predict the structure of alpha-helical coiled-coil proteins from their sequences, it is necessary to know how the side-chains pack in the interface between the alpha-helical strands. Since in alpha-fibrous proteins leucine is the most common residue at both the a and d positions of the heptad repeat, which form the inner core of the interface, we determined the lowest-energy conformation for a two-stranded coiled-coil with the sequence (LAALAAA)5. Coiled-coils were constructed using the Crick equations with a range of pitches, major helical radii and relative rotations of the two strands, and with different starting side-chain conformations. On energy minimisation, convergence occurred to a small number of structures. The lowest-energy coiled-coil had 2-fold rotational symmetry, an average pitch of 131 A and an average radius of 4.52 A; the leucine side-chain conformations were tt and g+t at the a and d positions. This coiled-coil was used as a former to determine the lowest-energy side-chain conformations for the 63 combinations of a and d residues that occur in the repeating heptad sequence of rat skeletal myosin. The leucine residues at the a and d positions of the central heptad were replaced by the a-d pair of interest and molecular dynamics simulations performed to allow the side-chains of these residues to explore conformational space. The lowest-energy side-chain conformation of a residue at an a or d position depends on the nature of the partnering residue, consistent with the fact that these side-chains pack against one another. In most cases the lowest-energy structure was symmetric but in a few cases the side-chains were asymmetrically disposed in the two strands. The local pitch is very sensitive to the nature of the residues in the inner core and varies over a twofold range. In contrast, the radius and relative rotation of the two strands were relatively insensitive to sequence.
Offer
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Department of Clinical Veterinary Science, University of Bristol, UK.
Sessions
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D000409:Alanine / Q000737:chemistry; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry; D001216:Asparagine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D003198:Computer Simulation; D003545:Cysteine / Q000737:chemistry; D005971:Glutamates / Q000737:chemistry; D005973:Glutamine / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D007532:Isoleucine / Q000737:chemistry; D007930:Leucine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D012694:Serine / Q000737:chemistry; D013816:Thermodynamics; D013912:Threonine / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry; D014633:Valine / Q000737:chemistry
D005971:Glutamates; D007532:Isoleucine; D005973:Glutamine; D013912:Threonine; D001224:Aspartic Acid; D014443:Tyrosine; D012694:Serine; D006639:Histidine; D001216:Asparagine; D001120:Arginine; D008715:Methionine; D007930:Leucine; D014633:Valine; D008239:Lysine; D003545:Cysteine; D000409:Alanine