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PDBsum entry 1yz8

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protein dna_rna links
Transcription/DNA PDB id
1yz8
Jmol
Contents
Protein chain
68 a.a. *
DNA/RNA
* Residue conservation analysis
Superseded by: 2lkx
PDB id:
1yz8
Name: Transcription/DNA
Title: Solution structure of the k50 class homeodomain pitx2 bound implications for mutations that cause rieger syndrome
Structure: Pituitary homeobox 2. Chain: p. Fragment: DNA-binding domain. Synonym: rieg bicoid-related homeobox transcription factor, solurshin, all1 responsive protein arp1. Engineered: yes. 5'-d( Gp Cp Tp Cp Tp Ap Ap Tp Cp Cp Cp Cp G)-3'. Chain: b. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: pitx2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic: yes
NMR struc: 20 models
Authors: B.A.Chaney,K.Clark-Baldwin,V.Dave,J.Ma,M.Rance
Key ref:
B.A.Chaney et al. (2005). Solution structure of the K50 class homeodomain PITX2 bound to DNA and implications for mutations that cause Rieger syndrome. Biochemistry, 44, 7497-7511. PubMed id: 15895993 DOI: 10.1021/bi0473253
Date:
28-Feb-05     Release date:   03-May-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q99697  (PITX2_HUMAN) -  Pituitary homeobox 2
Seq:
Struc:
317 a.a.
68 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 9 residue positions (black crosses)

 

 
DOI no: 10.1021/bi0473253 Biochemistry 44:7497-7511 (2005)
PubMed id: 15895993  
 
 
Solution structure of the K50 class homeodomain PITX2 bound to DNA and implications for mutations that cause Rieger syndrome.
B.A.Chaney, K.Clark-Baldwin, V.Dave, J.Ma, M.Rance.
 
  ABSTRACT  
 
We have determined the solution structure of a complex containing the K50 class homeodomain Pituitary homeobox protein 2 (PITX2) bound to its consensus DNA site (TAATCC). Previous studies have suggested that residue 50 is an important determinant of differential DNA-binding specificity among homeodomains. Although structures of several homeodomain-DNA complexes have been determined, this is the first structure of a native K50 class homeodomain. The only K50 homeodomain structure determined previously is an X-ray crystal structure of an altered specificity mutant, Engrailed Q50K (EnQ50K). Analysis of the NMR structure of the PITX2 homeodomain indicates that the lysine at position 50 makes contacts with two guanines on the antisense strand of the DNA, adjacent to the TAAT core DNA sequence, consistent with the structure of EnQ50K. Our evidence suggests that this side chain may make fluctuating interactions with the DNA, which is complementary to the crystal data for EnQ50K. There are differences in the tertiary structure between the native K50 structure and that of EnQ50K, which may explain differences in affinity and specificity between these proteins. Mutations in the human PITX2 gene are responsible for Rieger syndrome, an autosomal dominant disorder. Analysis of the residues mutated in Rieger syndrome indicates that many of these residues are involved in DNA binding, while others are involved in formation of the hydrophobic core of the protein. Overall, the role of K50 in homeodomain recognition is further clarified, and the results indicate that native K50 homeodomains may exhibit differences from altered specificity mutants.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21498098 S.Y.Yang, X.L.Yang, L.F.Yao, H.B.Wang, and C.K.Sun (2011).
Effect of CpG methylation on DNA binding protein: Molecular dynamics simulations of the homeodomain PITX2 bound to the methylated DNA.
  J Mol Graph Model, 29, 920-927.  
21052876 T.Doerdelmann, D.J.Kojetin, J.M.Baird-Titus, and M.Rance (2011).
(1)H, (13)C and (15)N chemical shift assignments for the human Pitx2 homeodomain and a R24H homeodomain mutant.
  Biomol NMR Assign, 5, 105-107.  
20084168 D.Becker, J.Tetens, A.Brunner, D.Bürstel, M.Ganter, J.Kijas, and C.Drögemüller (2010).
Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
  PLoS One, 5, e8689.  
20396904 L.Ashkenazi-Hoffnung, Y.Lebenthal, A.W.Wyatt, N.K.Ragge, S.Dateki, M.Fukami, T.Ogata, M.Phillip, and G.Gat-Yablonski (2010).
A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency.
  Hum Genet, 127, 721-729.  
19204119 B.J.Lesch, A.R.Gehrke, M.L.Bulyk, and C.I.Bargmann (2009).
Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans.
  Genes Dev, 23, 345-358.  
19106114 J.Fortin, P.Lamba, Y.Wang, and D.J.Bernard (2009).
Conservation of mechanisms mediating gonadotrophin-releasing hormone 1 stimulation of human luteinizing hormone beta subunit transcription.
  Mol Hum Reprod, 15, 77-87.  
18950742 C.A.Gurnett, F.Alaee, L.M.Kruse, D.M.Desruisseau, J.T.Hecht, C.A.Wise, A.M.Bowcock, and M.B.Dobbs (2008).
Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation.
  Am J Hum Genet, 83, 616-622.  
18854042 R.S.Mali, G.H.Peng, X.Zhang, L.Dang, S.Chen, and K.P.Mitton (2008).
FIZ1 is part of the regulatory protein complex on active photoreceptor-specific gene promoters in vivo.
  BMC Mol Biol, 9, 87.  
17914434 J.C.Sowden (2007).
Molecular and developmental mechanisms of anterior segment dysgenesis.
  Eye, 21, 1310-1318.  
17140726 T.F.Lerch, M.Xu, T.S.Jardetzky, K.E.Mayo, I.Radhakrishnan, R.Kazer, L.D.Shea, and T.K.Woodruff (2007).
The structures that underlie normal reproductive function.
  Mol Cell Endocrinol, 267, 1-5.  
16607563 G.Chatelain, N.Fossat, G.Brun, and T.Lamonerie (2006).
Molecular dissection reveals decreased activity and not dominant negative effect in human OTX2 mutants.
  J Mol Med, 84, 604-615.  
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.