SASDA85: CHD4 (PP-CC-AH-D) (Human Chromatin Remodeler CHD4 (363-1353))

Basic information

• Entry: Database: SASBDB / ID: SASDA85

Sample

CHD4 (PP-CC-AH-D)

• Human Chromatin Remodeler CHD4 (363-1353) (protein), CHD4 (PP-CC-AH-D), 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 #98: ; Type: dummy / Software: dammif / Radius of dummy atoms: 3.60 A / Chi-square value: 1.909924; Search similar-shape structures of this assembly by Omokage search (details)
• Model #102: ; Type: dummy / Software: monsa / Radius of dummy atoms: 5.00 A / Comment: Combined multiphase model / Chi-square value: 3.629025; Search similar-shape structures of this assembly by Omokage search (details)
• Model #103: ; Type: dummy / Software: monsa / Radius of dummy atoms: 5.00 A / Chi-square value: 3.629025; Search similar-shape structures of this assembly by Omokage search (details)
• Model #104: ; Type: dummy / Software: monsa / Radius of dummy atoms: 5.00 A / Chi-square value: 2.778889
• Model #105: ; Type: dummy / Software: monsa / Radius of dummy atoms: 5.00 A / Chi-square value: 1.098304; Search similar-shape structures of this assembly by Omokage search (details)
• Model #106: ; Type: dummy / Software: monsa / Radius of dummy atoms: 5.00 A / Chi-square value: 2.3716

Sample

• Sample: Name: CHD4 (PP-CC-AH-D) / Sample MW: 117.4 kDa / Specimen concentration: 1.00-8.30
• Buffer: Name: 50 mM HEPES / pH: 7.5 / Composition: 5.0% Glycerol, 300 mM NaCl

Entity #81

Name: CHD4 (PP-CC-AH-D) / Type: protein / Description: Human Chromatin Remodeler CHD4 (363-1353) / Formula weight: 117.4 / Num. of mol.: 1 / Source: Homo sapiens
Sequence:

MGHHHHHHSS GVDLGTENLY FQSMDGYETD HQDYCEVCQQ GGEIILCDTC PRAYHMVCLD PDMEKAPEGK WSCPHCEKEG IQWEAKEDNS EGEEILEEVG GDLEEEDDHH MEFCRVCKDG GELLCCDTCP SSYHIHCLNP PLPEIPNGEW LCPRCTCPAL KGKVQKILIW KWGQPPSPTP VPRPPDADPN TPSPKPLEGR PERQFFVKWQ GMSYWHCSWV SELQLELHCQ VMFRNYQRKN DMDEPPSGDF GGDEEKSRKR KNKDPKFAEM EERFYRYGIK PEWMMIHRIL NHSVDKKGHV HYLIKWRDLP YDQASWESED VEIQDYDLFK QSYWNHRELM RGEEGRPGKK LKKVKLRKLE RPPETPTVDP TVKYERQPEY LDATGGTLHP YQMEGLNWLR FSWAQGTDTI LADEMGLGKT VQTAVFLYSL YKEGHSKGPF LVSAPLSTII NWEREFEMWA PDMYVVTYVG DKDSRAIIRE NEFSFEDNAI RGGKKASRMK KEASVKFHVL LTSYELITID MAILGSIDWA CLIVDEAHRL KNNQSKFFRV LNGYSLQHKL LLTGTPLQNN LEELFHLLNF LTPERFHNLE GFLEEFADIA KEDQIKKLHD MLGPHMLRRL KADVFKNMPS KTELIVRVEL SPMQKKYYKY ILTRNFEALN ARGGGNQVSL LNVVMDLKKC CNHPYLFPVA AMEAPKMPNG MYDGSALIRA SGKLLLLQKM LKNLKEGGHR VLIFSQMTKM LDLLEDFLEH EGYKYERIDG GITGNMRQEA IDRFNAPGAQ QFCFLLSTRA GGLGINLATA DTVIIYDSDW NPHNDIQAFS RAHRIGQNKK VMIYRFVTRA SVEERITQVA KKKMMLTHLV VRPGLGSKTG SMSKQELDDI LKFGTEELFK DEATDGGGDN KEGEDSSVIH YDDKAIERLL DRNQDETEDT ELQGMNEYLS SFKVAQYVVR EEEMGEEEEV EREIIKQEES VDPDYWEKLL RHHYEQQQED LARNLGKGKR IRKQVNYNDG SQEDR

Experimental information

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

Scan

Title: CHD4 (PP-CC-AH-D) / 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	0.1356	6.0155

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 436 /

	Min	Max
Q	0.1356	1.327
P(R) point	29	464
R	0	17.36

Result

D max: 17.4 / 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	119 kDa	119 kDa

	Guinier	P(R)
Forward scattering, I0	109.38	-
Radius of gyration, Rg	4.9 nm	5 nm