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PDBsum entry 1u41
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Transcription
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PDB id
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1u41
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Snapshot of protein structure evolution reveals conservation of functional dimerization through intertwined folding.
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Authors
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D.Y.Chirgadze,
M.Demydchuk,
M.Becker,
S.Moran,
M.Paoli.
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Ref.
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Structure, 2004,
12,
1489-1494.
[DOI no: ]
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PubMed id
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Abstract
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Protein-protein interactions govern a wide range of cellular processes.
Molecular recognition responsible for homodimerization and heterodimerization in
the rel/NF-kappaB family of eukaryotic transcription factors relies on a small
cluster of hydrophobic residues. We have carried out a structural analysis of
six NF-kappaB p50 dimer interface mutants; one of them revealed a remarkable
alteration. One or possibly both its mutations cause a switch into an
intertwined dimer, in which the molecular partners exchange nearly half of their
fold. In spite of the extensive swapping of secondary structure elements, the
topology within each counterpart is preserved, with a very similar overall
structure and minimal changes at the interface. Thus intertwining rescues
structure and function from a destabilizing mutation. Since the mutants
originate from a directed evolution experiment and are functional, the data
provide an evolutionary snapshot of how a protein structure can respond to
mutations while maintaining a functional molecular architecture.
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Figure 1.
Figure 1. Schematic Representation of the Structure of the
NF-kB Dimerization Domains(A) The wild-type homodimeric
conformation and (B) the intertwined fold of the MLAM mutant are
shown. The mutations are Tyr267->Met and Val310->Met. Two loops
in the MLAM mutant that could not be built into the structure
due to disorder are labeled (residues from 285 to 290 in both
chains). The extensive intertwining between the two polypeptide
chains is responsible for excluding from the solvent a total
surface area of about 4600 Å2. Orthogonal views are shown.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
1489-1494)
copyright 2004.
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