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PDBsum entry 1k1a
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Transcription PDB id
1k1a

 

 

 

 

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Contents
Protein chain
228 a.a. *
Waters ×195
* Residue conservation analysis
PDB id:
1k1a
Name: Transcription
Title: Crystal structure of the ankyrin repeat domain of bcl-3: a unique member of the ikappab protein family
Structure: B-cell lymphoma 3-encoded protein. Chain: a. Fragment: ankyrin repeat domain. Synonym: bcl3, bcl-3 protein. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.86Å     R-factor:   0.200     R-free:   0.229
Authors: F.Michel,M.Soler-Lopez,C.Petosa,P.Cramer,U.Siebenlist,C.W.Mueller
Key ref:
F.Michel et al. (2001). Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family. EMBO J, 20, 6180-6190. PubMed id: 11707390 DOI: 10.1093/emboj/20.22.6180
Date:
24-Sep-01     Release date:   21-Nov-01    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P20749  (BCL3_HUMAN) -  B-cell lymphoma 3 protein from Homo sapiens
Seq:
Struc: 		454 a.a.
228 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1093/emboj/20.22.6180 EMBO J 20:6180-6190 (2001)
PubMed id: 11707390  
 
 
Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the IkappaB protein family.
F.Michel, M.Soler-Lopez, C.Petosa, P.Cramer, U.Siebenlist, C.W.Müller.
 
  ABSTRACT  
 
IkappaB proteins associate with the transcription factor NF-kappaB via their ankyrin repeat domain. Bcl-3 is an unusual IkappaB protein because it is primarily nucleoplasmic and can lead to enhanced NF-kappaB-dependent transcription, unlike the prototypical IkappaB protein IkappaBalpha, which inhibits NF-kappaB activity by retaining it in the cytoplasm. Here we report the 1.9 A crystal structure of the ankyrin repeat domain of human Bcl-3 and compare it with that of IkappaBalpha bound to NF-kappaB. The two structures are highly similar over the central ankyrin repeats but differ in the N-terminal repeat and at the C-terminus, where Bcl-3 contains a seventh repeat in place of the acidic PEST region of IkappaBalpha. Differences between the two structures suggest why Bcl-3 differs from IkappaBalpha in selectivity towards various NF-kappaB species, why Bcl-3 but not IkappaBalpha can associate with its NF-kappaB partner bound to DNA, and why two molecules of Bcl-3 but only one of IkappaBalpha can bind to its NF-kappaB partner. Comparison of the two structures thus provides an insight into the functional diversity of IkappaB proteins.
 
  Selected figure(s)  
 
Figure 4.
Figure 4 Comparison of Bcl-3 and I B molecular surfaces. The structures of I B (A, B, E and F) and Bcl-3 (C, D, G and H) are shown in equivalent orientations. The view of (A) -(D) is orthogonal to that of (E) -(H), which is approximately that of Figure 1B (i.e. with -hairpins on the left and 2 helices on the right.) (A, D, E and H) Comparison of electrostatic surface potentials. Regions of negative and positive potential are shown in red and blue, respectively. The basic patch at the bottom of Bcl-3 is formed by arginine residues 311, 318, 322, 342, 344, 345 and 351. The corresponding surface of I B is formed by the acidic PEST region. (B, C, F and G) Conservation of the NF- B contact surface. The C-terminal domains of p50 (blue) and p65 (green) are represented as ribbons bound to the surface of I B and, to facilitate comparison, to that of Bcl-3. In (B) and (F), regions of the I B surface within 4.5 Å of the p50 and p65 RHR-c domains are colored magenta. In (C) and (G), surface-exposed residues, which are identically conserved between Bcl-3 and I B , are shown in yellow. The asterisks and triangles indicate regions of the I B surface in contact with NF- B that are composed of residues poorly conserved in Bcl-3. This figure was prepared using GRASP (Nicholls et al., 1991). 		Figure 6.
Figure 6 Hypothetical model of Bcl-3 bound to a DNA-bound p50 homodimer. The model was constructed based on the structure of the I B -NF B complex, by structurally aligning Bcl-3 (yellow) onto I B (red) and a DNA-bound p50 homodimer (green and blue; Müller et al., 1995) onto the p50 -p65 heterodimer (not shown, although it is nearly identical to the p50 homodimer, where the green monomer corresponds to the p65 subunit). A 30-base pair stretch of ideal B-form DNA was then superimposed onto the shorter duplex present in the p50 -DNA crystal structure. (A) Side view showing that sufficient space is available next to the DNA to accommodate ANK repeat 7 of Bcl-3 but not the PEST region of I B . (B) View showing that the C-terminal domains of I B and Bcl-3 are positioned on opposite sides of the ARD. The view is that of (A) rotated by 110° about the vertical axis.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (2001, 20, 6180-6190) copyright 2001.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21472811 B.Manavalan, R.Govindaraj, G.Lee, and S.Choi (2011).
Molecular modeling-based evaluation of dual function of IκBζ ankyrin repeat domain in toll-like receptor signaling.
  J Mol Recognit, 24, 597-607.  
21135870 C.Zheng, Q.Yin, and H.Wu (2011).
Structural studies of NF-κB signaling.
  Cell Res, 21, 183-195.  
21203422 B.Manavalan, S.Basith, Y.M.Choi, G.Lee, and S.Choi (2010).
Structure-function relationship of cytoplasmic and nuclear IκB proteins: an in silico analysis.
  PLoS One, 5, e15782.  
19962898 S.Al-Khodor, C.T.Price, A.Kalia, and Y.Abu Kwaik (2010).
Functional diversity of ankyrin repeats in microbial proteins.
  Trends Microbiol, 18, 132-139.  
19806201 S.U.Ahmed, and J.Milner (2009).
Basal cancer cell survival involves JNK2 suppression of a novel JNK1/c-Jun/Bcl-3 apoptotic network.
  PLoS One, 4, e7305.  
  20066103 T.Huxford, and G.Ghosh (2009).
A structural guide to proteins of the NF-kappaB signaling module.
  Cold Spring Harbor Perspect Biol, 1, a000075.  
18279343 F.Habyarimana, S.Al-Khodor, A.Kalia, J.E.Graham, C.T.Price, M.T.Garcia, and Y.A.Kwaik (2008).
Role for the Ankyrin eukaryotic-like genes of Legionella pneumophila in parasitism of protozoan hosts and human macrophages.
  Environ Microbiol, 10, 1460-1474.  
  18811729 S.Al-Khodor, C.T.Price, F.Habyarimana, A.Kalia, and Y.Abu Kwaik (2008).
A Dot/Icm-translocated ankyrin protein of Legionella pneumophila is required for intracellular proliferation within human macrophages and protozoa.
  Mol Microbiol, 70, 908-923.  
17171436 F.Wang, J.Hu, P.Song, and W.Gong (2007).
Two novel transcripts encoding two Ankyrin repeat containing proteins have preponderant expression during the mouse spermatogenesis.
  Mol Biol Rep, 34, 249-260.  
16882997 C.J.McCleverty, E.Koesema, A.Patapoutian, S.A.Lesley, and A.Kreusch (2006).
Crystal structure of the human TRPV2 channel ankyrin repeat domain.
  Protein Sci, 15, 2201-2206.
PDB code: 2f37
16533741 H.Ohno, M.Nishikori, Y.Maesako, and H.Haga (2005).
Reappraisal of BCL3 as a molecular marker of anaplastic large cell lymphoma.
  Int J Hematol, 82, 397-405.  
16061795 H.Thoetkiattikul, M.H.Beck, and M.R.Strand (2005).
Inhibitor kappaB-like proteins from a polydnavirus inhibit NF-kappaB activation and suppress the insect immune response.
  Proc Natl Acad Sci U S A, 102, 11426-11431.  
  16511116 K.Yoneda, H.Sakuraba, H.Tsuge, N.Katunuma, S.Kuramitsu, T.Kawabata, and T.Ohshima (2005).
The first crystal structure of an archaeal helical repeat protein.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 636-639.
PDB code: 1wy6
14583612 B.Padmanabhan, N.Adachi, K.Kataoka, and M.Horikoshi (2004).
Crystal structure of the homolog of the oncoprotein gankyrin, an interactor of Rb and CDK4/6.
  J Biol Chem, 279, 1546-1552.
PDB code: 1ixv
15215520 C.H.Croy, S.Bergqvist, T.Huxford, G.Ghosh, and E.A.Komives (2004).
Biophysical characterization of the free IkappaBalpha ankyrin repeat domain in solution.
  Protein Sci, 13, 1767-1777.  
14573596 H.Pang, M.Bartlam, Q.Zeng, H.Miyatake, T.Hisano, K.Miki, L.L.Wong, G.F.Gao, and Z.Rao (2004).
Crystal structure of human pirin: an iron-binding nuclear protein and transcription cofactor.
  J Biol Chem, 279, 1491-1498.
PDB code: 1j1l
15152081 L.K.Mosavi, T.J.Cammett, D.C.Desrosiers, and Z.Y.Peng (2004).
The ankyrin repeat as molecular architecture for protein recognition.
  Protein Sci, 13, 1435-1448.  
15385955 N.Tanaka, M.Nakanishi, Y.Kusakabe, Y.Goto, Y.Kitade, and K.T.Nakamura (2004).
Structural basis for recognition of 2',5'-linked oligoadenylates by human ribonuclease L.
  EMBO J, 23, 3929-3938.
PDB code: 1wdy
15240830 S.Zelivianski, R.Glowacki, and M.F.Lin (2004).
Transcriptional activation of the human prostatic acid phosphatase gene by NF-kappaB via a novel hexanucleotide-binding site.
  Nucleic Acids Res, 32, 3566-3580.  
12566564 A.Kohl, H.K.Binz, P.Forrer, M.T.Stumpp, A.Plückthun, and M.G.Grütter (2003).
Designed to be stable: crystal structure of a consensus ankyrin repeat protein.
  Proc Natl Acad Sci U S A, 100, 1700-1705.
PDB code: 1mj0
12730195 N.Watanabe, S.Wachi, and T.Fujita (2003).
Identification and characterization of BCL-3-binding protein: implications for transcription and DNA repair or recombination.
  J Biol Chem, 278, 26102-26110.  
12686541 S.Malek, D.B.Huang, T.Huxford, S.Ghosh, and G.Ghosh (2003).
X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex.
  J Biol Chem, 278, 23094-23100.
PDB codes: 1k3z 1oy3
12644465 Y.Nam, A.P.Weng, J.C.Aster, and S.C.Blacklow (2003).
Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex.
  J Biol Chem, 278, 21232-21239.  
11976503 N.Adachi, B.Padmanabhan, K.Kataoka, K.Kijima, M.Yamaki, and M.Horikoshi (2002).
Purification, crystallization and preliminary X-ray diffraction analysis of yeast regulatory particle non-ATPase subunit 6 (Nas6p).
  Acta Crystallogr D Biol Crystallogr, 58, 859-860.  
12456646 P.Michaely, D.R.Tomchick, M.Machius, and R.G.Anderson (2002).
Crystal structure of a 12 ANK repeat stack from human ankyrinR.
  EMBO J, 21, 6387-6396.
PDB code: 1n11
  12538160 T.C.Mitchell, B.S.Thompson, J.O.Trent, and C.R.Casella (2002).
A short domain within Bcl-3 is responsible for its lymphocyte survival activity.
  Ann N Y Acad Sci, 975, 132-147.  
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.

 

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