PDBsum entry 1u41

Transcription

PDB id: 1u41

Contents

Protein chains

103 a.a. *

101 a.a. *

Waters ×385

* Residue conservation analysis

PDB id:

1u41

Name:

Transcription

Title:

Crystal structure 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

Protein chain

P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit from Mus musculus

Seq: 971 a.a.

Struc: 103 a.a.*

Protein chains

P25799  (NFKB1_MOUSE) -  Nuclear factor NF-kappa-B p105 subunit from Mus musculus

Seq: 971 a.a.

Struc: 101 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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 Å2. 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