PDBsum entry 2lfb

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protein links
DNA-binding PDB id
Protein chain
100 a.a. *
* Residue conservation analysis
PDB id:
Name: DNA-binding
Title: Homeodomain from rat liver lfb1/hnf1 transcription factor, nmr, 20 structures
Structure: Lfb1/hnf1 transcription factor. Chain: a. Fragment: DNA-binding domain, residues 0 - 99, homeodomain. Engineered: yes. Mutation: yes
Source: Rattus rattus. Black rat. Organism_taxid: 10117. Organ: liver. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 20 models
Authors: O.Schott,M.Billeter,B.Leiting,G.Wider,K.Wuthrich
Key ref:
O.Schott et al. (1997). The NMR solution structure of the non-classical homeodomain from the rat liver LFB1/HNF1 transcription factor. J Mol Biol, 267, 673-683. PubMed id: 9126845 DOI: 10.1006/jmbi.1997.0905
12-Dec-96     Release date:   12-Mar-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P15257  (HNF1A_RAT) -  Hepatocyte nuclear factor 1-alpha
628 a.a.
100 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 8 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     DNA binding     1 term  


DOI no: 10.1006/jmbi.1997.0905 J Mol Biol 267:673-683 (1997)
PubMed id: 9126845  
The NMR solution structure of the non-classical homeodomain from the rat liver LFB1/HNF1 transcription factor.
O.Schott, M.Billeter, B.Leiting, G.Wider, K.Wüthrich.
The nuclear magnetic resonance (NMR) solution structure of the non-classical homeodomain from the rat liver LFB1/HNF1 transcription factor was determined with the program DIANA from an input of 1356 nuclear Overhauser enhancement (NOE) upper distance constraints and 228 dihedral angle constraints collected using experiments with the unlabelled, the uniformly 15N-labelled and the uniformly 13C-labelled protein. Out of a group of 50 independently calculated conformers the 20 conformers with the smallest residual DIANA target function values were refined by energy minimization with the program OPAL and are used to represent the NMR structure. The average of the pairwise root-mean-square deviations (r.m.s.d.) of these 20 individual NMR conformers relative to the mean coordinates is 0.73 A (1 A = 0.1 nm) for the backbone atoms N, C(alpha) and C' of residues 15 to 82. The chain-terminal polypeptide segments 1-14 and 90-99 are disordered in solution. The globular fold contains three well-defined helices comprising the residues 19 to 29, 37 to 53 and 71 to 81, and the third helix is extended by a less well-ordered fourth helix with residues 82 to 89, which coincides with corresponding observations in "classical" homeodomains. Side-chain analysis resulted in 33 "best-defined" side-chains, with global displacements smaller than 1.1 A, and addition of these side-chains to the global superposition of residues 15 to 82 resulted in a r.m.s.d of 0.81 A. The protein contains two hydrophobic cores, one of which corresponds to the helical packing seen in classical homeodomains, while the other one stabilizes the conformation of the 21-residue insertion between helices II and III. The individual helices and their relative spatial arrangements are stabilized by a variety of structural motifs, which include medium-range and long-range hydrogen bonds and salt bridges. Detailed comparison with the Antennapedia homeodomain, and studies of the complex formation with an operator DNA half-site provided initial information on the DNA-binding mode of the LFB1/HNF1 homeodomain.
  Selected figure(s)  
Figure 6.
Figure 6. Hydrogen bonding interactions, salt bridges and cation.p interactions that stabilize the global fold of the LFB1/HNF1-homeodomain. Same presentation as in Figure 5. The following specific interactions are shown: the hydrogen bond H d2 Asn47.O0 Val69, cation- p interactions between the guanidinium group of Arg73 and the aromatic ring of Phe14, the hydrogen bond H e Gln26.O e Glu45, cation.p interactions between the gua- nidinium group of Arg81 and the aromatic rings of Trp77 and Tyr28, a salt bridge between the side-chains of Arg81 and Glu85, and a hydrogen bond O e Glu85. H Z Tyr28.
Figure 7.
Figure 7. Comparison of the NMR solution structure and the X-ray crystal structure of the LFB1/HNF1- homeodomains. The backbones of the mean solution structure and the crystal structure are shown as cyan and red tubes, respectively. Only residues 15 to 89 are shown, since the N and C-terminal ends 1 to 14 and 90 to 99 are disordered in solution, and have not been reported in the crystal structure. The 33 side-chains which are ``best-defined'' in the NMR structure (see footnote to Table 2) are shown in yellow for the solution structure and green for the crystal structure.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 267, 673-683) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
12355088 O.Bluteau, E.Jeannot, P.Bioulac-Sage, J.M.Marqués, J.F.Blanc, H.Bui, J.C.Beaudoin, D.Franco, C.Balabaud, P.Laurent-Puig, and J.Zucman-Rossi (2002).
Bi-allelic inactivation of TCF1 in hepatic adenomas.
  Nat Genet, 32, 312-315.  
12453420 Y.I.Chi, J.D.Frantz, B.C.Oh, L.Hansen, S.Dhe-Paganon, and S.E.Shoelson (2002).
Diabetes mutations delineate an atypical POU domain in HNF-1alpha.
  Mol Cell, 10, 1129-1137.
PDB code: 1ic8
10933814 T.Sprules, N.Green, M.Featherstone, and K.Gehring (2000).
Conformational changes in the PBX homeodomain and C-terminal extension upon binding DNA and HOX-derived YPWM peptides.
  Biochemistry, 39, 9943-9950.
PDB code: 1du6
10585442 M.Vaxillaire, A.Abderrahmani, P.Boutin, B.Bailleul, P.Froguel, M.Yaniv, and M.Pontoglio (1999).
Anatomy of a homeoprotein revealed by the analysis of human MODY3 mutations.
  J Biol Chem, 274, 35639-35646.  
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