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PDBsum entry 2k7s

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protein links
Transcription PDB id
2k7s
Jmol
Contents
Protein chain
119 a.a. *
* Residue conservation analysis
PDB id:
2k7s
Name: Transcription
Title: Human arnt c-terminal pas domain, 3 residue ib slip
Structure: Aryl hydrocarbon receptor nuclear translocator. Chain: a. Fragment: arnt pas-b. Synonym: arnt protein, dioxin receptor, nuclear translocator, hypoxia-inducible factor 1 beta, hif-1 beta. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: arnt. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: M.R.Evans,P.B.Card,K.H.Gardner
Key ref:
M.R.Evans et al. (2009). ARNT PAS-B has a fragile native state structure with an alternative beta-sheet register nearby in sequence space. Proc Natl Acad Sci U S A, 106, 2617-2622. PubMed id: 19196990 DOI: 10.1073/pnas.0808270106
Date:
20-Aug-08     Release date:   20-Jan-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P27540  (ARNT_HUMAN) -  Aryl hydrocarbon receptor nuclear translocator
Seq:
Struc:
 
Seq:
Struc:
789 a.a.
119 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     signal transduction   1 term 
  Biochemical function     signal transducer activity     1 term  

 

 
DOI no: 10.1073/pnas.0808270106 Proc Natl Acad Sci U S A 106:2617-2622 (2009)
PubMed id: 19196990  
 
 
ARNT PAS-B has a fragile native state structure with an alternative beta-sheet register nearby in sequence space.
M.R.Evans, P.B.Card, K.H.Gardner.
 
  ABSTRACT  
 
The aryl hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop-helix Period/ARNT/Single-minded (bHLH-PAS) protein that controls various biological pathways as part of dimeric transcriptional regulator complexes with other bHLH-PAS proteins. The two PAS domains within ARNT, PAS-A and PAS-B, are essential for the formation of these complexes because they mediate protein-protein interactions via residues located on their beta-sheet surfaces. While investigating the importance of residues in ARNT PAS-B involved in these interactions, we uncovered a point mutation (Y456T) on the solvent-exposed beta-sheet surface that allowed this domain to interconvert with a second, stable conformation. Although both conformations are present in equivalent quantities in the Y456T mutant, this can be shifted almost completely to either end point by additional mutations. A high-resolution solution structure of a mutant ARNT PAS-B domain stabilized in the new conformation revealed a 3-residue slip in register and accompanying inversion of the central Ibeta-strand. We have demonstrated that the new conformation has >100-fold lower in vitro affinity for its heterodimerization partner, hypoxia-inducible factor 2alpha PAS-B. We speculate that the pliability in beta-strand register is related to the flexibility required of ARNT to bind to several partners and, more broadly, to the abilities of some PAS domains to regulate their activities in response to small-molecule cofactors.
 
  Selected figure(s)  
 
Figure 2.
ARNT PAS-B can exist in two distinct conformations. (A) Widespread peak doubling is observed throughout ^15N-^1H HSQC spectra of Y456T ARNT PAS-B, as seen by comparison with spectra from the wild-type protein. Several doubled sites are highlighted with blue circles in the Y456T spectrum. (B) The E403 resonance from the Y456T ARNT mutant indicates two slowly exchanging conformations, but the relative populations of these can be perturbed by additional mutations. (C) Demonstration that conformations 1 and 2 are in equilibrium is provided by Mono Q separation of conformation 2 from a Y456T sample and monitoring the reestablishment of the equilibrium with extended incubation.
Figure 5.
Residues adopt a similar conformation in both structures. (A and B) Sequence (A) and structure (B) alignment of both mutant and wild-type Iβ strands. Shifted side chains adopt conformations of wild-type residues despite changes in identity or sequence. This is clearly seen by residue C459, where in the wild-type conformation it is buried in the core but in the mutant conformation, it slips 3 residues, becoming solvent-exposed and filling the space occupied by T462.
 
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21539773 M.T.Panteva, R.Salari, M.Bhattacharjee, and L.T.Chong (2011).
Direct Observations of Shifts in the β-Sheet Register of a Protein-Peptide Complex Using Explicit Solvent Simulations.
  Biophys J, 100, L50-L52.  
20630474 G.I.van Boxel, S.Holmes, L.Fugger, and E.Y.Jones (2010).
An alternative conformation of the T-cell receptor alpha constant region.
  J Mol Biol, 400, 828-837.  
20591649 P.N.Bryan, and J.Orban (2010).
Proteins that switch folds.
  Curr Opin Struct Biol, 20, 482-488.  
19906177 P.Slavny, R.Little, P.Salinas, T.A.Clarke, and R.Dixon (2010).
Quaternary structure changes in a second Per-Arnt-Sim domain mediate intramolecular redox signal relay in the NifL regulatory protein.
  Mol Microbiol, 75, 61-75.  
19836329 A.Möglich, R.A.Ayers, and K.Moffat (2009).
Structure and signaling mechanism of Per-ARNT-Sim domains.
  Structure, 17, 1282-1294.  
19722642 M.R.Evans, and K.H.Gardner (2009).
Slow transition between two beta-strand registers is dictated by protein unfolding.
  J Am Chem Soc, 131, 11306-11307.  
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.