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PDBsum entry 2ccf
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Four helix bundle
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PDB id
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2ccf
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References listed in PDB file
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Key reference
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Title
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Coiled coils at the edge of configurational heterogeneity. Structural analyses of parallel and antiparallel homotetrameric coiled coils reveal configurational sensitivity to a single solvent-Exposed amino acid substitution.
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Authors
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M.K.Yadav,
L.J.Leman,
D.J.Price,
C.L.Brooks,
C.D.Stout,
M.R.Ghadiri.
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Ref.
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Biochemistry, 2006,
45,
4463-4473.
[DOI no: ]
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PubMed id
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Abstract
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A detailed understanding of the mechanisms by which particular amino acid
sequences can give rise to more than one folded structure, such as for proteins
that undergo large conformational changes or misfolding, is a long-standing
objective of protein chemistry. Here, we describe the crystal structures of a
single coiled-coil peptide in distinct parallel and antiparallel tetrameric
configurations and further describe the parallel or antiparallel crystal
structures of several related peptide sequences; the antiparallel tetrameric
assemblies represent the first crystal structures of GCN4-derived peptides
exhibiting such a configuration. Intriguingly, substitution of a single
solvent-exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to
populate the antiparallel configuration, suggesting that the two configurations
are close enough in energy for subtle sequence changes to have important
structural consequences. We present a structural analysis of the small changes
to the helix register and side-chain conformations that accommodate the two
configurations and have supplemented these results using solution studies and a
molecular dynamics energetic analysis using a replica exchange methodology.
Considering the previous examples of structural nonspecificity in coiled-coil
peptides, the findings reported here not only emphasize the predisposition of
the coiled-coil motif to adopt multiple configurations but also call attention
to the associated risk that observed crytstal structures may not represent the
only (or even the major) species present in solution.
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