Protein plasticity to the extreme: changing the topology of a 4-alpha-helical bundle with a single amino acid substitution.
BACKGROUND
Conventional wisdom has it that two proteins sharing 98.4% sequence identity have nearly identical three-dimensional structures. Here we provide a counter-example to this statement by showing that a single amino acid substitution can change the topology of a homodimeric 4-alpha-helical bundle protein.


RESULTS
We have determined the high-resolution crystal structure of a 4-alpha-helical protein with a single alanine to proline mutation in the turn region, and show that this single amino acid substitution leads to a complete reorganisation of the whole molecule. The protein is converted from the canonical left-handed all-antiparallel form, to a right-handed mixed parallel and antiparallel bundle, which to the best of our knowledge and belief represents a novel topological motif for this class of proteins.


CONCLUSIONS
The results suggest a possible new mechanism for the creation and evolution of topological motifs, show the importance of loop regions in determining the allowable folding pathways, and illustrate the malleability of protein structures.
Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, Heraklion, Crete, Greece.
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Glykos
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Cesareni
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Kokkinidis
D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D019281:Dimerization; D008958:Models, Molecular; D009154:Mutation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D055672:Static Electricity; D013816:Thermodynamics
D001426:Bacterial Proteins; D016601:RNA-Binding Proteins; C054243:Rop protein, ColE1 plasmid