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PDBsum entry 1u41

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protein Protein-protein interface(s) links
Transcription PDB id
1u41
Jmol
Contents
Protein chains
103 a.a. *
101 a.a. *
Waters ×385
* Residue conservation analysis
PDB id:
1u41
Name: Transcription
Title: Crystal stucture of ylgv mutant of dimerisation domain of nf-kb p50 transcription factor
Structure: Nuclear factor nf-kappa-b p105 subunit. Chain: a, b, c, d. Fragment: dimerization domain. Synonym: nf-kb p50 transcription factor. DNA-binding factor kbf1. Ebp- 1. Nf-kappa-b1 p84/nf-kappa-b1 p98 [contains: nuclear factor nf- kappa-b p50 subunit]. Engineered: yes. Mutation: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Gene: nfkb1, 18033. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.176     R-free:   0.235
Authors: D.Y.Chirgadze,M.Demydchuk,M.Becker,S.Moran,M.Paoli
Key ref:
D.Y.Chirgadze et al. (2004). Snapshot of protein structure evolution reveals conservation of functional dimerization through intertwined folding. Structure, 12, 1489-1494. PubMed id: 15296742 DOI: 10.1016/j.str.2004.06.011
Date:
23-Jul-04     Release date:   17-Aug-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit
Seq:
Struc:
 
Seq:
Struc:
971 a.a.
103 a.a.*
Protein chains
Pfam   ArchSchema ?
P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit
Seq:
Struc:
 
Seq:
Struc:
971 a.a.
101 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     regulation of transcription, DNA-dependent   1 term 
  Biochemical function     sequence-specific DNA binding transcription factor activity     1 term  

 

 
DOI no: 10.1016/j.str.2004.06.011 Structure 12:1489-1494 (2004)
PubMed id: 15296742  
 
 
Snapshot of protein structure evolution reveals conservation of functional dimerization through intertwined folding.
D.Y.Chirgadze, M.Demydchuk, M.Becker, S.Moran, M.Paoli.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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 2. Orthogonal views are shown.
 
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1489-1494) copyright 2004.  
  Figure was selected by the author.  
 
 
    Author's comment    
 
  The transcription factor NF-kappaB relies on dimerisation for its function. Its dimerisation interface is relatively small, and is dominated by a cluster of hydrophobic residues (4 per monomer). Structural elucidation of one functional interface mutant showed how the plasticity of protein architecture can sometimes rescue function from a potentially lethal mutation.


The structure of this NF-kappaB mutant reveals a striking change which is best defined an intertwined folding. Whilst the two monomers still associate in the native-like way, they have exchange nearly half of their fold, with their polypeptide chains effectively intertwining with one another. Remarkably, the overall structure of the dimer remains unchanged in the mutant relative to the wild type, thus explaining how the mutant retains its functionality.


Max Paoli
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19768810 S.Wang, O.Kirillova, M.Chruszcz, D.Gront, M.D.Zimmerman, M.T.Cymborowski, I.A.Shumilin, T.Skarina, E.Gorodichtchenskaia, A.Savchenko, A.M.Edwards, and W.Minor (2009).
The crystal structure of the AF2331 protein from Archaeoglobus fulgidus DSM 4304 forms an unusual interdigitated dimer with a new type of alpha + beta fold.
  Protein Sci, 18, 2410-2419.
PDB code: 2fdo
16680196 P.Wong, and D.Frishman (2006).
Fold designability, distribution, and disease.
  PLoS Comput Biol, 2, e40.  
16154093 D.B.Huang, D.Vu, and G.Ghosh (2005).
NF-kappaB RelB forms an intertwined homodimer.
  Structure, 13, 1365-1373.
PDB codes: 1zk9 1zka
15296726 M.J.Bennett, and D.Eisenberg (2004).
The evolving role of 3D domain swapping in proteins.
  Structure, 12, 1339-1341.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.