4W5A

Complex structure of ATRX ADD bound to H3K9me3S10ph peptide

Summary for 4W5A

• Entry DOI: 10.2210/pdb4w5a/pdb
• Related: 3QL9 3QLA 3QLC 3QLN
• Descriptor: Transcriptional regulator ATRX, Peptide from Histone H3.3, ZINC ION, ... (4 entities in total)
• Functional Keywords: epigenetic regulation, complex, transcription, mitosis, hydrolase-structural protein complex, hydrolase/structural protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P46100 P84243
• Total number of polymer chains: 6
• Total formula weight: 50033.86

Authors

Zhao, D.,Xiang, B.,Li, H. (deposition date: 2014-08-17, release date: 2015-01-21, Last modification date: 2023-11-08)

Primary citation

Noh, K.M.,Maze, I.,Zhao, D.,Xiang, B.,Wenderski, W.,Lewis, P.W.,Shen, L.,Li, H.,Allis, C.D.
ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons
Proc.Natl.Acad.Sci.USA, 112:6820-6827, 2015

PubMed Abstract: ATRX (the alpha thalassemia/mental retardation syndrome X-linked protein) is a member of the switch2/sucrose nonfermentable2 (SWI2/SNF2) family of chromatin-remodeling proteins and primarily functions at heterochromatic loci via its recognition of "repressive" histone modifications [e.g., histone H3 lysine 9 tri-methylation (H3K9me3)]. Despite significant roles for ATRX during normal neural development, as well as its relationship to human disease, ATRX function in the central nervous system is not well understood. Here, we describe ATRX's ability to recognize an activity-dependent combinatorial histone modification, histone H3 lysine 9 tri-methylation/serine 10 phosphorylation (H3K9me3S10ph), in postmitotic neurons. In neurons, this "methyl/phos" switch occurs exclusively after periods of stimulation and is highly enriched at heterochromatic repeats associated with centromeres. Using a multifaceted approach, we reveal that H3K9me3S10ph-bound Atrx represses noncoding transcription of centromeric minor satellite sequences during instances of heightened activity. Our results indicate an essential interaction between ATRX and a previously uncharacterized histone modification in the central nervous system and suggest a potential role for abnormal repetitive element transcription in pathological states manifested by ATRX dysfunction.

PubMed: 25538301
DOI: 10.1073/pnas.1411258112

Experimental method

X-RAY DIFFRACTION (2.6 Å)