PDBsum entry 3ql9

Transcription/structural protein

PDB id: 3ql9

Contents

Protein chain

125 a.a.

Ligands

ALA-ARG-THR-LYS-GLN-THR-ALA-ARG-M3L-SER

Metals

_ZN ×3

Waters ×240

PDB id:

3ql9

Name:

Transcription/structural protein

Title:

Monoclinic complex structure of atrx add bound to histone h3k9me3 peptide

Structure:

Transcriptional regulator atrx. Chain: a. Fragment: n-terminal add domain, unp residues 167-289. Synonym: atp-dependent helicase atrx, x-linked helicase ii, x-linked nuclear protein, xnp, znf-hx. Engineered: yes. Mutation: yes. Peptide of histone h3.3. Chain: c.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: atrx, rad54l, xh2. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: this sequence occurs naturally in humans

Resolution:

0.93Å R-factor: 0.123 R-free: 0.131

Authors:

B.Xiang,H.Li

Key ref:

S.Iwase et al. (2011). ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome. Nat Struct Biol, 18, 769-776. PubMed id: 21666679

Date:

02-Feb-11 Release date: 15-Jun-11

Protein chain

P46100  (ATRX_HUMAN) -  Transcriptional regulator ATRX from Homo sapiens

Seq: 2492 a.a.

Struc: 125 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.6.4.12 - Dna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nat Struct Biol 18:769-776 (2011)

PubMed id: 21666679

ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome.

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, Y.Shi.

ABSTRACT

ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD(ATRX)), whose function has remained elusive. Here we identify ADD(ATRX) as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD(ATRX) bound to H3(1-15)K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.