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.
PDB ID: 1B6QDownload
MMDB ID: 55445
PDB Deposition Date: 1999/1/16
Updated in MMDB: 2011/11
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
Similar Structures:
Biological Unit for 1B6Q: dimeric; determined by author and by software (PISA,PQS)
Molecular Components in 1B6Q
Label Count Molecule
Proteins (2 molecules)
ROP(Gene symbol: rom)
Molecule annotation
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Citing MMDB