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PDBsum entry 2ld1
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protein metals links
Metal binding protein PDB id
2ld1

 

 

 

 

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Contents
Protein chain
142 a.a.
Metals
_ZN ×3
PDB id:
2ld1
Name: Metal binding protein
Title: Structures and chemical shift assignments for the add domain of the atrx protein
Structure: Transcriptional regulator atrx. Chain: a. Fragment: add domain, residues 159-296. Synonym: atp-dependent helicase atrx, x-linked helicase ii, x-linked nuclear protein, xnp, znf-hx. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: atrx, rad54l, xh2. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 34 models
Authors: D.Neuhaus,J.Yang
Key ref: A.Argentaro et al. (2007). Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX. Proc Natl Acad Sci U S A, 104, 11939-11944. PubMed id: 17609377
Date:
13-May-11     Release date:   08-Jun-11    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P46100  (ATRX_HUMAN) -  Transcriptional regulator ATRX from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		2492 a.a.
142 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.12  - Dna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate + H+
ATP
 + H2O
 = ADP
 + phosphate
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Proc Natl Acad Sci U S A 104:11939-11944 (2007)
PubMed id: 17609377  
 
 
Structural consequences of disease-causing mutations in the ATRX-DNMT3-DNMT3L (ADD) domain of the chromatin-associated protein ATRX.
A.Argentaro, J.C.Yang, L.Chapman, M.S.Kowalczyk, R.J.Gibbons, D.R.Higgs, D.Neuhaus, D.Rhodes.
 
  ABSTRACT  
 
The chromatin-associated protein ATRX was originally identified because mutations in the ATRX gene cause a severe form of syndromal X-linked mental retardation associated with alpha-thalassemia. Half of all of the disease-associated missense mutations cluster in a cysteine-rich region in the N terminus of ATRX. This region was named the ATRX-DNMT3-DNMT3L (ADD) domain, based on sequence homology with a family of DNA methyltransferases. Here, we report the solution structure of the ADD domain of ATRX, which consists of an N-terminal GATA-like zinc finger, a plant homeodomain finger, and a long C-terminal alpha-helix that pack together to form a single globular domain. Interestingly, the alpha-helix of the GATA-like finger is exposed and highly basic, suggesting a DNA-binding function for ATRX. The disease-causing mutations fall into two groups: the majority affect buried residues and hence affect the structural integrity of the ADD domain; another group affects a cluster of surface residues, and these are likely to perturb a potential protein interaction site. The effects of individual point mutations on the folding state and stability of the ADD domain correlate well with the levels of mutant ATRX protein in patients, providing insights into the molecular pathophysiology of ATR-X syndrome.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21421568 A.Dhayalan, R.Tamas, I.Bock, A.Tattermusch, E.Dimitrova, S.Kudithipudi, S.Ragozin, and A.Jeltsch (2011).
The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9.
  Hum Mol Genet, 20, 2195-2203.  
21505078 M.Mitson, L.A.Kelley, M.J.Sternberg, D.R.Higgs, and R.J.Gibbons (2011).
Functional significance of mutations in the Snf2 domain of ATRX.
  Hum Mol Genet, 20, 2603-2610.  
21427128 S.Bagheri-Fam, A.Argentaro, T.Svingen, A.N.Combes, A.H.Sinclair, P.Koopman, and V.R.Harley (2011).
Defective survival of proliferating Sertoli cells and androgen receptor function in a mouse model of the ATR-X syndrome.
  Hum Mol Genet, 20, 2213-2224.  
21666677 S.Eustermann, J.C.Yang, M.J.Law, R.Amos, L.M.Chapman, C.Jelinska, D.Garrick, D.Clynes, R.J.Gibbons, D.Rhodes, D.R.Higgs, and D.Neuhaus (2011).
Combinatorial readout of histone H3 modifications specifies localization of ATRX to heterochromatin.
  Nat Struct Mol Biol, 18, 777-782.
PDB code: 2lbm
21666679 S.Iwase, B.Xiang, S.Ghosh, T.Ren, P.W.Lewis, J.C.Cochrane, C.D.Allis, D.J.Picketts, D.J.Patel, H.Li, and Y.Shi (2011).
ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome.
  Nat Struct Mol Biol, 18, 769-776.
PDB codes: 3ql9 3qla 3qlc 3qln
  21339843 H.Hashimoto, P.M.Vertino, and X.Cheng (2010).
Molecular coupling of DNA methylation and histone methylation.
  Epigenomics, 2, 657-669.  
21029854 I.Whitehouse, and T.Owen-Hughes (2010).
ATRX: Put me on repeat.
  Cell, 143, 335-336.  
20110566 L.H.Wong, J.D.McGhie, M.Sim, M.A.Anderson, S.Ahn, R.D.Hannan, A.J.George, K.A.Morgan, J.R.Mann, and K.H.Choo (2010).
ATRX interacts with H3.3 in maintaining telomere structural integrity in pluripotent embryonic stem cells.
  Genome Res, 20, 351-360.  
21029860 M.J.Law, K.M.Lower, H.P.Voon, J.R.Hughes, D.Garrick, V.Viprakasit, M.Mitson, M.De Gobbi, M.Marra, A.Morris, A.Abbott, S.P.Wilder, S.Taylor, G.M.Santos, J.Cross, H.Ayyub, S.Jones, J.Ragoussis, D.Rhodes, I.Dunham, D.R.Higgs, and R.J.Gibbons (2010).
ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner.
  Cell, 143, 367-378.  
20602808 V.Barresi, A.Ragusa, M.Fichera, N.Musso, L.Castiglia, G.Rappazzo, S.Travali, T.Mattina, C.Romano, G.Cocchi, and D.F.Condorelli (2010).
Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome.
  BMC Med Genomics, 3, 28.  
20147399 V.Lukashchuk, and R.D.Everett (2010).
Regulation of ICP0-null mutant herpes simplex virus type 1 infection by ND10 components ATRX and hDaxx.
  J Virol, 84, 4026-4040.  
19444090 A.Jezela-Stanek, C.Fisher, M.Szarras-Czapnik, D.Olczak-Kowalczyk, R.J.Gibbons, J.Słowikowska-Hilczer, and M.Krajewska-Walasek (2009).
X-linked alpha thalassaemia/mental retardation syndrome: a case with gonadal dysgenesis, caused by a novel mutation in ATRX gene.
  Clin Dysmorphol, 18, 168-171.  
19834512 J.Otani, T.Nankumo, K.Arita, S.Inamoto, M.Ariyoshi, and M.Shirakawa (2009).
Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX-DNMT3-DNMT3L domain.
  EMBO Rep, 10, 1235-1241.
PDB codes: 3a1a 3a1b
19833297 R.G.Urdinguio, J.V.Sanchez-Mut, and M.Esteller (2009).
Epigenetic mechanisms in neurological diseases: genes, syndromes, and therapies.
  Lancet Neurol, 8, 1056-1072.  
18682256 L.A.Baker, C.D.Allis, and G.G.Wang (2008).
PHD fingers in human diseases: disorders arising from misinterpreting epigenetic marks.
  Mutat Res, 647, 3.  
18409179 R.J.Gibbons, T.Wada, C.A.Fisher, N.Malik, M.J.Mitson, D.P.Steensma, A.Fryer, D.R.Goudie, I.D.Krantz, and J.Traeger-Synodinos (2008).
Mutations in the chromatin-associated protein ATRX.
  Hum Mutat, 29, 796-802.  
18922870 V.Lukashchuk, S.McFarlane, R.D.Everett, and C.M.Preston (2008).
Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection.
  J Virol, 82, 12543-12554.  
17984965 S.D.Taverna, H.Li, A.J.Ruthenburg, C.D.Allis, and D.J.Patel (2007).
How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers.
  Nat Struct Mol Biol, 14, 1025-1040.  
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.

 

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