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DNA binding protein PDB id
1kw4
Jmol
Contents
Protein chain
70 a.a. *
Waters ×56
* Residue conservation analysis
PDB id:
1kw4
Name: DNA binding protein
Title: Polyhomeotic sam domain structure
Structure: Polyhomeotic. Chain: a. Fragment: sam domain. Engineered: yes. Mutation: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.75Å     R-factor:   0.220     R-free:   0.234
Authors: C.A.Kim,M.Gingery,R.M Pilpa,J.U.Bowie
Key ref:
C.A.Kim et al. (2002). The SAM domain of polyhomeotic forms a helical polymer. Nat Struct Biol, 9, 453-457. PubMed id: 11992127 DOI: 10.1038/nsb802
Date:
28-Jan-02     Release date:   05-Jun-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P39769  (PHP_DROME) -  Polyhomeotic-proximal chromatin protein
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1589 a.a.
70 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1038/nsb802 Nat Struct Biol 9:453-457 (2002)
PubMed id: 11992127  
 
 
The SAM domain of polyhomeotic forms a helical polymer.
C.A.Kim, M.Gingery, R.M.Pilpa, J.U.Bowie.
 
  ABSTRACT  
 
The polycomb group (PcG) proteins are important in the maintenance of stable repression patterns during development. Several PcG members contain a protein protein interaction module called a SAM domain (also known as SPM, PNT and HLH). Here we report the high-resolution structure of the SAM domain of polyhomeotic (Ph). Ph-SAM forms a helical polymer structure, providing a likely mechanism for the extension of PcG complexes. The structure of the polymer resembles that formed by the SAM domain of another transcriptional repressor, TEL. The formation of these polymer structures by SAM domains in two divergent repressors suggests a conserved mode of repression involving a higher order chromatin structure.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Electron micrograph of Ph-SAM. 		Figure 2.
Figure 2. Polymeric structure of Ph-SAM L51R. a, Nine subunits of the polymer viewed with the helix axis in the plane of the paper. b, Same as (a) but viewed down the polymer helix axis. c, A view of the interface. Each subunit of the polymer is shaded in alternating colors. The residues comprising the apolar domain are yellow, with the exception of the L51R mutant side chain (gold). The atoms of the polar domain are colored as follows: oxygen (red), nitrogen (blue), backbone carbon (black) and water oxygen (magenta). d, A closer view of the hydrogen bonds and salt bridges at the interface.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 453-457) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20048052 J.Zhang, T.G.Graham, P.Vivekanand, L.Cote, M.Cetera, and I.Rebay (2010).
Sterile alpha motif domain-mediated self-association plays an essential role in modulating the activity of the Drosophila ETS family transcriptional repressor Yan.
  Mol Cell Biol, 30, 1158-1170.  
20150898 S.M.Di Pietro, D.Cascio, D.Feliciano, J.U.Bowie, and G.S.Payne (2010).
Regulation of clathrin adaptor function in endocytosis: novel role for the SAM domain.
  EMBO J, 29, 1033-1044.
PDB code: 3idw
20979614 V.Prieto-Echagüe, A.Gucwa, D.A.Brown, and W.T.Miller (2010).
Regulation of Ack1 localization and activity by the amino-terminal SAM domain.
  BMC Biochem, 11, 42.  
18618697 A.Bhunia, P.N.Domadia, H.Mohanram, and S.Bhattacharjya (2009).
NMR structural studies of the Ste11 SAM domain in the dodecyl phosphocholine micelle.
  Proteins, 74, 328-343.  
18831011 A.D.Meruelo, and J.U.Bowie (2009).
Identifying polymer-forming SAM domains.
  Proteins, 74, 1-5.  
19636380 G.N.Maertens, S.El Messaoudi-Aubert, T.Racek, J.K.Stock, J.Nicholls, M.Rodriguez-Niedenführ, J.Gil, and G.Peters (2009).
Several distinct polycomb complexes regulate and co-localize on the INK4a tumor suppressor locus.
  PLoS One, 4, e6380.  
19765305 M.Leone, J.Cellitti, and M.Pellecchia (2009).
The Sam domain of the lipid phosphatase Ship2 adopts a common model to interact with Arap3-Sam and EphA2-Sam.
  BMC Struct Biol, 9, 59.
PDB code: 2kg5
19754893 P.B.Stathopulos, and M.Ikura (2009).
Structurally delineating stromal interaction molecules as the endoplasmic reticulum calcium sensors and regulators of calcium release-activated calcium entry.
  Immunol Rev, 231, 113-131.  
19401562 S.Shen, J.Lau, M.Zhu, J.Zou, D.Fuller, Q.J.Li, and W.Zhang (2009).
The importance of Src homology 2 domain-containing leukocyte phosphoprotein of 76 kilodaltons sterile-alpha motif domain in thymic selection and T-cell activation.
  Blood, 114, 74-84.  
18991394 M.Leone, J.Cellitti, and M.Pellecchia (2008).
NMR studies of a heterotypic Sam-Sam domain association: the interaction between the lipid phosphatase Ship2 and the EphA2 receptor.
  Biochemistry, 47, 12721-12728.
PDB code: 2k4p
18854159 P.B.Stathopulos, L.Zheng, G.Y.Li, M.J.Plevin, and M.Ikura (2008).
Structural and mechanistic insights into STIM1-mediated initiation of store-operated calcium entry.
  Cell, 135, 110-122.
PDB code: 2k60
18422744 R.Kanno, H.Janakiraman, and M.Kanno (2008).
Epigenetic regulator polycomb group protein complexes control cell fate and cancer.
  Cancer Sci, 99, 1077-1084.  
18287031 T.Rajakulendran, M.Sahmi, I.Kurinov, M.Tyers, M.Therrien, and F.Sicheri (2008).
CNK and HYP form a discrete dimer by their SAM domains to mediate RAF kinase signaling.
  Proc Natl Acad Sci U S A, 105, 2836-2841.
PDB codes: 3bs5 3bs7
17001316 A.M.Deshpande, J.D.Akunowicz, X.T.Reveles, B.B.Patel, E.A.Saria, R.G.Gorlick, S.L.Naylor, R.J.Leach, and M.F.Hansen (2007).
PHC3, a component of the hPRC-H complex, associates with E2F6 during G0 and is lost in osteosarcoma tumors.
  Oncogene, 26, 1714-1722.  
17430569 G.Ausiello, D.Peluso, A.Via, and M.Helmer-Citterich (2007).
Local comparison of protein structures highlights cases of convergent evolution in analogous functional sites.
  BMC Bioinformatics, 8, S24.  
17322404 K.D.Baker, R.B.Beckstead, D.J.Mangelsdorf, and C.S.Thummel (2007).
Functional interactions between the Moses corepressor and DHR78 nuclear receptor regulate growth in Drosophila.
  Genes Dev, 21, 450-464.  
17825942 S.J.Whitcomb, A.Basu, C.D.Allis, and E.Bernstein (2007).
Polycomb Group proteins: an evolutionary perspective.
  Trends Genet, 23, 494-502.  
17088907 C.Rimkus, M.Martini, J.Friederichs, R.Rosenberg, D.Doll, J.R.Siewert, B.Holzmann, and K.P.Janssen (2006).
Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.
  Br J Cancer, 95, 1419-1423.  
16543225 C.Wu, G.Jansen, J.Zhang, D.Y.Thomas, and M.Whiteway (2006).
Adaptor protein Ste50p links the Ste11p MEKK to the HOG pathway through plasma membrane association.
  Genes Dev, 20, 734-746.  
16362034 F.Qiao, B.Harada, H.Song, J.Whitelegge, A.J.Courey, and J.U.Bowie (2006).
Mae inhibits Pointed-P2 transcriptional activity by blocking its MAPK docking site.
  EMBO J, 25, 70-79.  
16600911 J.Y.Roignant, S.Hamel, F.Janody, and J.E.Treisman (2006).
The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway.
  Genes Dev, 20, 795-806.  
16429151 T.Aviv, Z.Lin, G.Ben-Ari, C.A.Smibert, and F.Sicheri (2006).
Sequence-specific recognition of RNA hairpins by the SAM domain of Vts1p.
  Nat Struct Mol Biol, 13, 168-176.
PDB code: 2f8k
16539743 T.Inoue, K.Terada, A.Furukawa, C.Koike, Y.Tamaki, M.Araie, and T.Furukawa (2006).
Cloning and characterization of mr-s, a novel SAM domain protein, predominantly expressed in retinal photoreceptor cells.
  BMC Dev Biol, 6, 15.  
15905166 C.A.Kim, M.R.Sawaya, D.Cascio, W.Kim, and J.U.Bowie (2005).
Structural organization of a Sex-comb-on-midleg/polyhomeotic copolymer.
  J Biol Chem, 280, 27769-27775.
PDB codes: 1pk1 1pk3
15563468 J.W.Voncken, H.Niessen, B.Neufeld, U.Rennefahrt, V.Dahlmans, N.Kubben, B.Holzer, S.Ludwig, and U.R.Rapp (2005).
MAPKAP kinase 3pK phosphorylates and regulates chromatin association of the polycomb group protein Bmi1.
  J Biol Chem, 280, 5178-5187.  
16024804 K.Isono, Y.Fujimura, J.Shinga, M.Yamaki, J.O-Wang, Y.Takihara, Y.Murahashi, Y.Takada, Y.Mizutani-Koseki, and H.Koseki (2005).
Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate polycomb repression of Hox genes.
  Mol Cell Biol, 25, 6694-6706.  
15689513 S.Bhattacharjya, P.Xu, M.Chakrapani, L.Johnston, and F.Ni (2005).
Polymerization of the SAM domain of MAPKKK Ste11 from the budding yeast: implications for efficient signaling through the MAPK cascades.
  Protein Sci, 14, 828-835.  
15280237 A.J.Peterson, D.R.Mallin, N.J.Francis, C.S.Ketel, J.Stamm, R.K.Voeller, R.E.Kingston, and J.A.Simon (2004).
Requirement for sex comb on midleg protein interactions in Drosophila polycomb group repression.
  Genetics, 167, 1225-1239.  
15143160 C.E.Tognon, C.D.Mackereth, A.M.Somasiri, L.P.McIntosh, and P.H.Sorensen (2004).
Mutations in the SAM domain of the ETV6-NTRK3 chimeric tyrosine kinase block polymerization and transformation activity.
  Mol Cell Biol, 24, 4636-4650.  
15260987 F.Qiao, H.Song, C.A.Kim, M.R.Sawaya, J.B.Hunter, M.Gingery, I.Rebay, A.J.Courey, and J.U.Bowie (2004).
Derepression by depolymerization; structural insights into the regulation of Yan by Mae.
  Cell, 118, 163-173.
PDB codes: 1sv0 1sv4
15107848 H.Zhang, G.A.Smolen, R.Palmer, A.Christoforou, S.van den Heuvel, and D.A.Haber (2004).
SUMO modification is required for in vivo Hox gene regulation by the Caenorhabditis elegans Polycomb group protein SOP-2.
  Nat Genet, 36, 507-511.  
15314179 J.Y.Ali, and W.Bender (2004).
Cross-regulation among the polycomb group genes in Drosophila melanogaster.
  Mol Cell Biol, 24, 7737-7747.  
15568982 L.Ringrose, and R.Paro (2004).
Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins.
  Annu Rev Genet, 38, 413-443.  
15509784 M.De Rycker, and C.M.Price (2004).
Tankyrase polymerization is controlled by its sterile alpha motif and poly(ADP-ribose) polymerase domains.
  Mol Cell Biol, 24, 9802-9812.  
14967148 M.Lavigne, N.J.Francis, I.F.King, and R.E.Kingston (2004).
Propagation of silencing; recruitment and repression of naive chromatin in trans by polycomb repressed chromatin.
  Mol Cell, 13, 415-425.  
14573615 S.J.Grimshaw, H.R.Mott, K.M.Stott, P.R.Nielsen, K.A.Evetts, L.J.Hopkins, D.Nietlispach, and D.Owen (2004).
Structure of the sterile alpha motif (SAM) domain of the Saccharomyces cerevisiae mitogen-activated protein kinase pathway-modulating protein STE50 and analysis of its interaction with the STE11 SAM.
  J Biol Chem, 279, 2192-2201.
PDB code: 1uqv
12515807 E.Astoul, A.D.Laurence, N.Totty, S.Beer, D.R.Alexander, and D.A.Cantrell (2003).
Approaches to define antigen receptor-induced serine kinase signal transduction pathways.
  J Biol Chem, 278, 9267-9275.  
12820967 J.B.Green, C.D.Gardner, R.P.Wharton, and A.K.Aggarwal (2003).
RNA recognition via the SAM domain of Smaug.
  Mol Cell, 11, 1537-1548.
PDB code: 1oxj
12588862 P.Boccuni, D.MacGrogan, J.M.Scandura, and S.D.Nimer (2003).
The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6).
  J Biol Chem, 278, 15412-15420.  
14732928 R.L.Rich, and D.G.Myszka (2003).
A survey of the year 2002 commercial optical biosensor literature.
  J Mol Recognit, 16, 351-382.  
12858164 T.Aviv, Z.Lin, S.Lau, L.M.Rendl, F.Sicheri, and C.A.Smibert (2003).
The RNA-binding SAM domain of Smaug defines a new family of post-transcriptional regulators.
  Nat Struct Biol, 10, 614-621.  
12942139 T.M.Hall (2003).
SAM breaks its stereotype.
  Nat Struct Biol, 10, 677-679.  
12702867 T.Pawson, and P.Nash (2003).
Assembly of cell regulatory systems through protein interaction domains.
  Science, 300, 445-452.  
  12414187 K.A.Dean, A.K.Aggarwal, and R.P.Wharton (2002).
Translational repressors in Drosophila.
  Trends Genet, 18, 572-577.  
12171939 R.Ramachander, C.A.Kim, M.L.Phillips, C.D.Mackereth, C.D.Thanos, L.P.McIntosh, and J.U.Bowie (2002).
Oligomerization-dependent association of the SAM domains from Schizosaccharomyces pombe Byr2 and Ste4.
  J Biol Chem, 277, 39585-39593.  
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 code is shown on the right.