SASDAA5: CHD4 (AH) (Human Chromatin Remodeler CHD4 (685-1233))

Basic information

• Entry: Database: SASBDB / ID: SASDAA5

Sample

CHD4 (AH)

• Human Chromatin Remodeler CHD4 (685-1233) (protein), CHD4 (AH), Homo sapiens

• Biological species: Homo sapiens (human)
• Citation: Journal: J Mol Biol / Year: 2012; Title: The PHD and chromo domains regulate the ATPase activity of the human chromatin remodeler CHD4.; Authors: Aleksandra A Watson / Pravin Mahajan / Haydyn D T Mertens / Michael J Deery / Wenchao Zhang / Peter Pham / Xiuxia Du / Till Bartke / Wei Zhang / Christian Edlich / Georgina Berridge / Yun Chen / Nicola A Burgess-Brown / Tony Kouzarides / Nicola Wiechens / Tom Owen-Hughes / Dmitri I Svergun / Opher Gileadi / Ernest D Laue / ; Abstract: The NuRD (nucleosome remodeling and deacetylase) complex serves as a crucial epigenetic regulator of cell differentiation, proliferation, and hematopoietic development by coupling the deacetylation and demethylation of histones, nucleosome mobilization, and the recruitment of transcription factors. The core nucleosome remodeling function of the mammalian NuRD complex is executed by the helicase-domain-containing ATPase CHD4 (Mi-2β) subunit, which also contains N-terminal plant homeodomain (PHD) and chromo domains. The mode of regulation of chromatin remodeling by CHD4 is not well understood, nor is the role of its PHD and chromo domains. Here, we use small-angle X-ray scattering, nucleosome binding ATPase and remodeling assays, limited proteolysis, cross-linking, and tandem mass spectrometry to propose a three-dimensional structural model describing the overall shape and domain interactions of CHD4 and discuss the relevance of these for regulating the remodeling of chromatin by the NuRD complex.

Contact author

• Haydyn Mertens (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

Models

• Model #100: ; Type: dummy / Software: dammif / Radius of dummy atoms: 1.90 A / Chi-square value: 1.592644; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: CHD4 (AH) / Sample MW: 62.8 kDa / Specimen concentration: 1.40-8.60
• Buffer: Name: HEPES / Concentration: 50.00 mM / PK: 7 / pH: 7.5 / Comment: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid / Composition: KCl 50.000 mM

Entity #84

Name: CHD4 (AH) / Type: protein / Description: Human Chromatin Remodeler CHD4 (685-1233) / Formula weight: 62.8 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

MPGKKLKKVK LRKLERPPET PTVDPTVKYE RQPEYLDATG GTLHPYQMEG LNWLRFSWAQ GTDTILADEM GLGKTVQTAV FLYSLYKEGH SKGPFLVSAP LSTIINWERE FEMWAPDMYV VTYVGDKDSR AIIRENEFSF EDNAIRGGKK ASRMKKEASV KFHVLLTSYE LITIDMAILG SIDWACLIVD EAHRLKNNQS KFFRVLNGYS LQHKLLLTGT PLQNNLEELF HLLNFLTPER FHNLEGFLEE FADIAKEDQI KKLHDMLGPH MLRRLKADVF KNMPSKTELI VRVELSPMQK KYYKYILTRN FEALNARGGG NQVSLLNVVM DLKKCCNHPY LFPVAAMEAP KMPNGMYDGS ALIRASGKLL LLQKMLKNLK EGGHRVLIFS QMTKMLDLLE DFLEHEGYKY ERIDGGITGN MRQEAIDRFN APGAQQFCFL LSTRAGGLGI NLATADTVII YDSDWNPHND IQAFSRAHRI GQNKKVMIYR FVTRASVEER ITQVAKKKMM LTHLVVRPGL GSKTGSMSKQ ELDDILKFGT EELFKDEATD

Experimental information

• Beam: Instrument name: DORIS III X33 / City: Hamburg / 国: Germany / Shape: 0.6 / Type of source: X-ray synchrotron / Wavelength: 0.15 Å / Dist. spec. to detc.: 2.7 mm
• Detector: Name: Pilatus 1M-W / Pixsize x: 0.172 mm

Scan

Title: CHD4 (AH) / Measurement date: Nov 13, 2010 / Storage temperature: 10 °C / Cell temperature: 10 °C / Exposure time: 15 sec. / Number of frames: 8 / Unit: 1/nm /

	Min	Max
Q	0.1985	6.0155

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 302 /

	Min	Max
Q	0.1998	1.847
P(R) point	52	353
R	0	13.22

Result

Type of curve: extrapolated / Standard: BSA
Comments: The ATPase CHD4 mediates nucleosome remodeling by the NuRD (nucleosome remodeling and deacetylase) complex. The NuRD complex serves as a crucial epigenetic regulator of cell differentiation, proliferation, and hematopoietic development by coupling the deacetylation and demethylation of histones, nucleosome mobilization, and the recruitment of transcription factors. The three dimensional small-angle X-ray scattering model of CHD4 helps to define its interdomain interactions, with cross linking and limited proteolysis studies used to validate the model. Functional and binding assays suggest a regulatory role for the PHD and chromo domains.

	Experimental	Standard
MW	52 kDa	52 kDa

	Guinier	P(R)
Forward scattering, I0	45.63	-
Radius of gyration, Rg	4 nm	4.2 nm

	Min	Max
D	-	14.5
Guinier point	1	52