PDBsum entry 1ofc

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Nuclear protein PDB id
Protein chain
267 a.a. *
Waters ×48
* Residue conservation analysis
PDB id:
Name: Nuclear protein
Title: Nucleosome recognition module of iswi atpase
Structure: Iswi protein. Chain: x. Fragment: nucleosome recognition module (c-terminal third) residues 691-991. Synonym: imitation swi protein, nucleosome remodeling factor 140 kda subunit, nurf-140, chrac 140 kda subunit. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 469008.
1.90Å     R-factor:   0.219     R-free:   0.253
Authors: T.Grune,C.W.Muller
Key ref:
T.Grüne et al. (2003). Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI. Mol Cell, 12, 449-460. PubMed id: 14536084 DOI: 10.1016/S1097-2765(03)00273-9
10-Apr-03     Release date:   05-Sep-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q24368  (ISWI_DROME) -  Chromatin-remodeling complex ATPase chain Iswi
1027 a.a.
267 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   2 terms 
  Biological process     chromatin remodeling   2 terms 
  Biochemical function     nucleic acid binding     7 terms  


DOI no: 10.1016/S1097-2765(03)00273-9 Mol Cell 12:449-460 (2003)
PubMed id: 14536084  
Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI.
T.Grüne, J.Brzeski, A.Eberharter, C.R.Clapier, D.F.Corona, P.B.Becker, C.W.Müller.
Energy-dependent nucleosome remodeling emerges as a key process endowing chromatin with dynamic properties. However, the principles by which remodeling ATPases interact with their nucleosome substrate to alter histone-DNA interactions are only poorly understood. We have identified a substrate recognition domain in the C-terminal half of the remodeling ATPase ISWI and determined its structure by X-ray crystallography. The structure comprises three domains, a four-helix domain with a novel fold and two alpha-helical domains related to the modules of c-Myb, SANT and SLIDE, which are linked by a long helix. An integrated structural and functional analysis of these domains provides insight into how ISWI interacts with the nucleosomal substrate.
  Selected figure(s)  
Figure 3.
Figure 3. Structure of ISWI-C.
(A) Two orthogonal views of ISWI-C. The HAND domain is depicted in blue, SANT domain in green, SLIDE domain in yellow, and the spacer helix connecting the SANT and SLIDE domains in red. Disordered loops are depicted in gray. (A), (C), and Figures 4A and 4C were produced with the programs Molscript (Kraulis, 1991) and Raster3D (Merritt and Bacon, 1997).
(B) Sequence alignment of ISWI homologs from Drosophila melanogaster (dmISWI), human (hSNF2H), yeast (scIsw1p), the Arabidopsis thaliana homolog At5g18620 (atISWI), and the SANT domain of yeast Ada2p. Conserved and conservatively substituted residues are highlighted in blue. The secondary structure elements of the dmISWI structure are indicated. SANT and SLIDE domains as predicted by program SMART are underlined; brackets correspond to the deletion mutants SANT and SLIDE. Dashed lines indicate disordered regions.
(C) Electrostatic surface representation of ISWI-C. Depicted are the surfaces pointing away from the nucleosome (I) and facing it (II) in the hypothetical nucleosome/ISWI-C model described in the Discussion.
Figure 4.
Figure 4. Comparison of SANT and SLIDE Domains with DNA Binding Modules of c-Myb.
(A) Stereo diagram of the CA-backbones of SANT (green, rmsd27CA = 1.2Å) and SLIDE (yellow, rmsd34CA = 1.1Å) domain superimposed with DNA-bound repeat R3 of c-Myb (red). For the SANT domain only helixes SA1 and SA3 were used in the superposition.
(B) Structural sequence alignment of SANT and SLIDE domain with DNA binding modules R2 and R3 of c-Myb. Residues in SANT and SLIDE which allow similar contacts as in c-Myb modules R2 and R3 are indicated by green dots. Residues which do not allow similar contacts are indicated by red squares. Residues in c-Myb modules R2 and R3 contacting DNA bases and DNA backbone are highlighted in blue and yellow, respectively. Conserved and conservatively substituted residues are depicted on a light blue background.
(C) Models of hypothetical complexes of SANT (left) and SLIDE (right) bound to DNA based on the superposition of both domains onto c-Myb repeat R3. Residues compatible and incompatible with DNA binding are depicted in green and red, respectively. In (B) the corresponding residues are marked by red squares or green spheres.
  The above figures are reprinted by permission from Cell Press: Mol Cell (2003, 12, 449-460) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23288358 B.J.Manning, and C.L.Peterson (2013).
Releasing the brakes on a chromatin-remodeling enzyme.
  Nat Struct Mol Biol, 20, 5-7.  
23202585 F.Mueller-Planitz, H.Klinker, J.Ludwigsen, and P.B.Becker (2013).
The ATPase domain of ISWI is an autonomous nucleosome remodeling machine.
  Nat Struct Mol Biol, 20, 82-89.  
23334290 S.K.Hota, S.K.Bhardwaj, S.Deindl, Y.C.Lin, X.Zhuang, and B.Bartholomew (2013).
Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains.
  Nat Struct Mol Biol, 20, 222-229.  
23143334 C.R.Clapier, and B.R.Cairns (2012).
Regulation of ISWI involves inhibitory modules antagonized by nucleosomal epitopes.
  Nature, 492, 280-284.  
21443626 A.Feller, K.Machemer, E.L.Braun, and E.Grotewold (2011).
Evolutionary and comparative analysis of MYB and bHLH plant transcription factors.
  Plant J, 66, 94.  
21525927 K.Yamada, T.D.Frouws, B.Angst, D.J.Fitzgerald, C.DeLuca, K.Schimmele, D.F.Sargent, and T.J.Richmond (2011).
Structure and mechanism of the chromatin remodelling factor ISW1a.
  Nature, 472, 448-453.
PDB codes: 2y9y 2y9z
20974961 F.Erdel, T.Schubert, C.Marth, G.Längst, and K.Rippe (2010).
Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites.
  Proc Natl Acad Sci U S A, 107, 19873-19878.  
21172662 L.Lan, A.Ui, S.Nakajima, K.Hatakeyama, M.Hoshi, R.Watanabe, S.M.Janicki, H.Ogiwara, T.Kohno, S.Kanno, and A.Yasui (2010).
The ACF1 complex is required for DNA double-strand break repair in human cells.
  Mol Cell, 40, 976-987.  
20204433 M.N.Cruickshank, P.Besant, and D.Ulgiati (2010).
The impact of histone post-translational modifications on developmental gene regulation.
  Amino Acids, 39, 1087-1105.  
19531742 A.M.Baker, Q.Fu, W.Hayward, S.M.Lindsay, and T.M.Fletcher (2009).
The Myb/SANT domain of the telomere-binding protein TRF2 alters chromatin structure.
  Nucleic Acids Res, 37, 5019-5031.  
19956593 A.Neves-Costa, W.R.Will, A.T.Vetter, J.R.Miller, and P.Varga-Weisz (2009).
The SNF2-family member Fun30 promotes gene silencing in heterochromatic loci.
  PLoS One, 4, e8111.  
19355820 C.R.Clapier, and B.R.Cairns (2009).
The biology of chromatin remodeling complexes.
  Annu Rev Biochem, 78, 273-304.  
19395587 H.S.Pereira, A.Barão, A.Caperta, J.Rocha, W.Viegas, and M.Delgado (2009).
Rye Bs disclose ancestral sequences in cereal genomes with a potential role in gametophyte chromatid segregation.
  Mol Biol Evol, 26, 1683-1697.  
20008562 H.Yokoyama, S.Rybina, R.Santarella-Mellwig, I.W.Mattaj, and E.Karsenti (2009).
ISWI is a RanGTP-dependent MAP required for chromosome segregation.
  J Cell Biol, 187, 813-829.  
19528957 L.M.Figueiredo, G.A.Cross, and C.J.Janzen (2009).
Epigenetic regulation in African trypanosomes: a new kid on the block.
  Nat Rev Microbiol, 7, 504-513.  
20033039 L.R.Racki, J.G.Yang, N.Naber, P.D.Partensky, A.Acevedo, T.J.Purcell, R.Cooke, Y.Cheng, and G.J.Narlikar (2009).
The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes.
  Nature, 462, 1016-1021.  
19273607 M.Pinskaya, A.Nair, D.Clynes, A.Morillon, and J.Mellor (2009).
Nucleosome remodeling and transcriptional repression are distinct functions of Isw1 in Saccharomyces cerevisiae.
  Mol Cell Biol, 29, 2419-2430.  
18067919 A.E.Roche, B.J.Bassett, S.A.Samant, W.Hong, G.A.Blobel, and E.C.Svensson (2008).
The zinc finger and C-terminal domains of MTA proteins are required for FOG-2-mediated transcriptional repression via the NuRD complex.
  J Mol Cell Cardiol, 44, 352-360.  
18922045 A.Sala, G.La Rocca, G.Burgio, E.Kotova, D.Di Gesù, M.Collesano, A.M.Ingrassia, A.V.Tulin, and D.F.Corona (2008).
The nucleosome-remodeling ATPase ISWI is regulated by poly-ADP-ribosylation.
  PLoS Biol, 6, e252.  
18840288 E.R.Ko, D.Ko, C.Chen, and J.S.Lipsick (2008).
A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding.
  Mol Cancer, 7, 77.  
19043594 L.Wang, and C.C.Tsai (2008).
Atrophin proteins: an overview of a new class of nuclear receptor corepressors.
  Nucl Recept Signal, 6, e009.  
18814851 M.Hu, Y.B.Zhang, L.Qian, R.P.Briñas, L.Kuznetsova, and J.F.Hainfeld (2008).
Three-dimensional structure of human chromatin accessibility complex hCHRAC by electron microscopy.
  J Struct Biol, 164, 263-269.  
18321528 S.J.Johnson, D.Close, H.Robinson, I.Vallet-Gely, S.L.Dove, and C.P.Hill (2008).
Crystal structure and RNA binding of the Tex protein from Pseudomonas aeruginosa.
  J Mol Biol, 377, 1460-1473.
PDB codes: 3bzc 3bzk
18755760 S.Maheshwari, J.Wang, and D.A.Barbash (2008).
Recurrent positive selection of the Drosophila hybrid incompatibility gene Hmr.
  Mol Biol Evol, 25, 2421-2430.  
18174918 B.Manavathi, K.Singh, and R.Kumar (2007).
MTA family of coregulators in nuclear receptor biology and pathology.
  Nucl Recept Signal, 5, e010.  
17142453 B.Manavathi, and R.Kumar (2007).
Metastasis tumor antigens, an emerging family of multifaceted master coregulators.
  J Biol Chem, 282, 1529-1533.  
17984961 B.R.Cairns (2007).
Chromatin remodeling: insights and intrigue from single-molecule studies.
  Nat Struct Mol Biol, 14, 989-996.  
17255092 D.H.Sohn, K.Y.Lee, C.Lee, J.Oh, H.Chung, S.H.Jeon, and R.H.Seong (2007).
SRG3 interacts directly with the major components of the SWI/SNF chromatin remodeling complex and protects them from proteasomal degradation.
  J Biol Chem, 282, 10614-10624.  
17713580 E.Brown, S.Malakar, and J.E.Krebs (2007).
How many remodelers does it take to make a brain? Diverse and cooperative roles of ATP-dependent chromatin-remodeling complexes in development.
  Biochem Cell Biol, 85, 444-462.  
17377988 J.R.Horton, S.J.Elgar, S.I.Khan, X.Zhang, P.A.Wade, and X.Cheng (2007).
Structure of the SANT domain from the Xenopus chromatin remodeling factor ISWI.
  Proteins, 67, 1198-1202.
PDB code: 2nog
17431399 K.Hughes, M.Wand, L.Foulston, R.Young, K.Harley, S.Terry, K.Ersfeld, and G.Rudenko (2007).
A novel ISWI is involved in VSG expression site downregulation in African trypanosomes.
  EMBO J, 26, 2400-2410.  
17925393 M.A.Holbert, T.Sikorski, J.Carten, D.Snowflack, S.Hodawadekar, and R.Marmorstein (2007).
The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting.
  J Biol Chem, 282, 36603-36613.
PDB code: 2rc4
17362198 M.D.Shahbazian, and M.Grunstein (2007).
Functions of site-specific histone acetylation and deacetylation.
  Annu Rev Biochem, 76, 75.  
17506634 M.R.Singleton, M.S.Dillingham, and D.B.Wigley (2007).
Structure and mechanism of helicases and nucleic acid translocases.
  Annu Rev Biochem, 76, 23-50.  
17760996 R.Ferreira, A.Eberharter, T.Bonaldi, M.Chioda, A.Imhof, and P.B.Becker (2007).
Site-specific acetylation of ISWI by GCN5.
  BMC Mol Biol, 8, 73.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
17283061 V.K.Gangaraju, and B.Bartholomew (2007).
Dependency of ISW1a chromatin remodeling on extranucleosomal DNA.
  Mol Cell Biol, 27, 3217-3225.  
17306844 V.K.Gangaraju, and B.Bartholomew (2007).
Mechanisms of ATP dependent chromatin remodeling.
  Mutat Res, 618, 3.  
17908792 W.Dang, and B.Bartholomew (2007).
Domain architecture of the catalytic subunit in the ISW2-nucleosome complex.
  Mol Cell Biol, 27, 8306-8317.  
17496903 X.Yang, R.Zaurin, M.Beato, and C.L.Peterson (2007).
Swi3p controls SWI/SNF assembly and ATP-dependent H2A-H2B displacement.
  Nat Struct Mol Biol, 14, 540-547.  
16723979 A.Saha, J.Wittmeyer, and B.R.Cairns (2006).
Chromatin remodelling: the industrial revolution of DNA around histones.
  Nat Rev Mol Cell Biol, 7, 437-447.  
16461455 G.Da, J.Lenkart, K.Zhao, R.Shiekhattar, B.R.Cairns, and R.Marmorstein (2006).
Structure and function of the SWIRM domain, a conserved protein module found in chromatin regulatory complexes.
  Proc Natl Acad Sci U S A, 103, 2057-2062.
PDB code: 2fq3
16935875 H.Dürr, A.Flaus, T.Owen-Hughes, and K.P.Hopfner (2006).
Snf2 family ATPases and DExx box helicases: differences and unifying concepts from high-resolution crystal structures.
  Nucleic Acids Res, 34, 4160-4167.  
16821138 K.Bouazoune, and A.Brehm (2006).
ATP-dependent chromatin remodeling complexes in Drosophila.
  Chromosome Res, 14, 433-449.  
16885027 M.Yang, C.B.Gocke, X.Luo, D.Borek, D.R.Tomchick, M.Machius, Z.Otwinowski, and H.Yu (2006).
Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase.
  Mol Cell, 23, 377-387.
PDB code: 2iw5
16531230 N.Tochio, T.Umehara, S.Koshiba, M.Inoue, T.Yabuki, M.Aoki, E.Seki, S.Watanabe, Y.Tomo, M.Hanada, M.Ikari, M.Sato, T.Terada, T.Nagase, O.Ohara, M.Shirouzu, A.Tanaka, T.Kigawa, and S.Yokoyama (2006).
Solution structure of the SWIRM domain of human histone demethylase LSD1.
  Structure, 14, 457-468.
PDB code: 2com
16917504 T.Alenghat, J.Yu, and M.A.Lazar (2006).
The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor.
  EMBO J, 25, 3966-3974.  
15837933 A.Codina, J.D.Love, Y.Li, M.A.Lazar, D.Neuhaus, and J.W.Schwabe (2005).
Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors.
  Proc Natl Acad Sci U S A, 102, 6009-6014.
PDB code: 1xc5
15797201 B.R.Cairns (2005).
Chromatin remodeling complexes: strength in diversity, precision through specialization.
  Curr Opin Genet Dev, 15, 185-190.  
16094444 C.N.Johnson, N.L.Adkins, and P.Georgel (2005).
Chromatin remodeling complexes: ATP-dependent machines in action.
  Biochem Cell Biol, 83, 405-417.  
15832170 H.B.Hartman, J.Yu, T.Alenghat, T.Ishizuka, and M.A.Lazar (2005).
The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3.
  EMBO Rep, 6, 445-451.  
15882619 H.Dürr, C.Körner, M.Müller, V.Hickmann, and K.P.Hopfner (2005).
X-ray structures of the Sulfolobus solfataricus SWI2/SNF2 ATPase core and its complex with DNA.
  Cell, 121, 363-373.
PDB codes: 1z5z 1z63 1z6a
16223721 K.Bouazoune, and A.Brehm (2005).
dMi-2 chromatin binding and remodeling activities are regulated by dCK2 phosphorylation.
  J Biol Chem, 280, 41912-41920.  
16260604 K.F.Hartlepp, C.Fernández-Tornero, A.Eberharter, T.Grüne, C.W.Müller, and P.B.Becker (2005).
The histone fold subunits of Drosophila CHRAC facilitate nucleosome sliding through dynamic DNA interactions.
  Mol Cell Biol, 25, 9886-9896.
PDB codes: 2byk 2bym
15808743 L.Aravind, V.Anantharaman, S.Balaji, M.M.Babu, and L.M.Iyer (2005).
The many faces of the helix-turn-helix domain: transcription regulation and beyond.
  FEMS Microbiol Rev, 29, 231-262.  
16227570 T.G.Fazzio, M.E.Gelbart, and T.Tsukiyama (2005).
Two distinct mechanisms of chromatin interaction by the Isw2 chromatin remodeling complex in vivo.
  Mol Cell Biol, 25, 9165-9174.  
16195416 X.Mo, E.Kowenz-Leutz, Y.Laumonnier, H.Xu, and A.Leutz (2005).
Histone H3 tail positioning and acetylation by the c-Myb but not the v-Myb DNA-binding SANT domain.
  Genes Dev, 19, 2447-2457.  
15666348 la Cruz, S.Lois, S.Sánchez-Molina, and M.A.Martínez-Balbás (2005).
Do protein motifs read the histone code?
  Bioessays, 27, 164-175.  
15457208 A.Eberharter, I.Vetter, R.Ferreira, and P.B.Becker (2004).
ACF1 improves the effectiveness of nucleosome mobilization by ISWI through PHD-histone contacts.
  EMBO J, 23, 4029-4039.  
15196463 A.Flaus, and T.Owen-Hughes (2004).
Mechanisms for ATP-dependent chromatin remodelling: farewell to the tuna-can octamer?
  Curr Opin Genet Dev, 14, 165-173.  
16117649 C.B.Millar, S.K.Kurdistani, and M.Grunstein (2004).
Acetylation of yeast histone H4 lysine 16: a switch for protein interactions in heterochromatin and euchromatin.
  Cold Spring Harb Symp Quant Biol, 69, 193-200.  
15040448 L.A.Boyer, R.R.Latek, and C.L.Peterson (2004).
The SANT domain: a unique histone-tail-binding module?
  Nat Rev Mol Cell Biol, 5, 158-163.  
15184976 M.J.Bottomley (2004).
Structures of protein domains that create or recognize histone modifications.
  EMBO Rep, 5, 464-469.  
15131696 M.N.Kagalwala, B.J.Glaus, W.Dang, M.Zofall, and B.Bartholomew (2004).
Topography of the ISW2-nucleosome complex: insights into nucleosome spacing and chromatin remodeling.
  EMBO J, 23, 2092-2104.  
16117660 P.B.Becker (2004).
The chromatin accessibility complex: chromatin dynamics through nucleosome sliding.
  Cold Spring Harb Symp Quant Biol, 69, 281-287.  
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 codes are shown on the right.