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PDBsum entry 1hlo

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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
1hlo
Jmol
Contents
Protein chains
80 a.a. *
73 a.a. *
DNA/RNA
Waters ×18
* Residue conservation analysis
PDB id:
1hlo
Name: Transcription/DNA
Title: The crystal structure of an intact human max-DNA complex: new insights into mechanisms of transcriptional control
Structure: DNA (5'-d( Cp Ap Cp Cp Ap Cp Gp Tp Gp Gp T)-3'). Chain: c. Engineered: yes. DNA (5'-d( Ap Cp Cp Ap Cp Gp Tp Gp Gp Tp G)-3'). Chain: d. Engineered: yes. Protein (transcription factor max). Chain: a, b. Engineered: yes
Source: Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Octamer (from PQS)
Resolution:
2.80Å     R-factor:   0.213     R-free:   0.273
Authors: P.Brownlie,T.A.Ceska,M.Lamers,C.Romier,H.Theo,D.Suck
Key ref:
P.Brownlie et al. (1997). The crystal structure of an intact human Max-DNA complex: new insights into mechanisms of transcriptional control. Structure, 5, 509-520. PubMed id: 9115440 DOI: 10.1016/S0969-2126(97)00207-4
Date:
10-Sep-97     Release date:   27-Oct-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P61244  (MAX_HUMAN) -  Protein max
Seq:
Struc:
160 a.a.
80 a.a.
Protein chain
Pfam   ArchSchema ?
P61244  (MAX_HUMAN) -  Protein max
Seq:
Struc:
160 a.a.
73 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     protein dimerization activity     1 term  

 

 
DOI no: 10.1016/S0969-2126(97)00207-4 Structure 5:509-520 (1997)
PubMed id: 9115440  
 
 
The crystal structure of an intact human Max-DNA complex: new insights into mechanisms of transcriptional control.
P.Brownlie, T.Ceska, M.Lamers, C.Romier, G.Stier, H.Teo, D.Suck.
 
  ABSTRACT  
 
BACKGROUND: Max belongs to the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. Max is able to form homodimers and heterodimers with other members of this family, which include Mad, Mxi1 and Myc; Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E box) and rearrangement amongst these dimer forms provides a complex system of transcriptional regulation. Max is also regulated by phosphorylation at a site preceding the basic region. We report here the first crystal structure of an intact bHLHZ protein bound to its target site. RESULTS: The X-ray crystal structure of the intact human Max protein homodimer in complex with a 13-mer DNA duplex was determined to 2.8 A resolution and refined to an R factor of 0.213. The C-terminal domains in both chains of the Max dimer are disordered. In contrast to the DNA observed in complex with other bHLH and bHLHZ proteins, the DNA in the Max complex is bent by about 25 degrees, directed towards the protein. Intimate contacts with interdigitating sidechains give rise to the formation of tetramers in the crystal. CONCLUSIONS: The structure confirms the importance of the HLH and leucine zipper motifs in dimerization as well as the mode of E box recognition which was previously analyzed by X-ray crystallography of shortened constructs. The disorder observed in the C-terminal domain suggests that contacts with additional protein components of the transcription machinery are necessary for ordering the secondary structure. The tetramers seen in the crystal are consistent with the tendency of Max and other bHLHZ and HLH proteins to form higher order oligomers in solution and may play a role in DNA looping. The location of the two phosphorylation sites at Ser1 and Ser10 (the latter is the N-cap of the basic helix) suggests how phosphorylation could disrupt DNA binding.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. A stereo view superposition of intact Max (this study), MyoD and truncated Max (from the Burley study) showing the overlap of the three structures. Max from this study is in green, MyoD is shown in magenta and Max from Burley's group [10] is shown in blue.
 
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 509-520) copyright 1997.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
20627128 C.Y.Chou, C.H.Hsu, Y.H.Wang, M.Y.Chang, L.C.Chen, S.C.Cheng, and Y.H.Chen (2011).
Biochemical and structural properties of zebrafish Capsulin produced by Escherichia coli.
  Protein Expr Purif, 75, 21-27.  
20236989 M.A.Schumacher, K.M.Piro, and W.Xu (2010).
Insight into F plasmid DNA segregation revealed by structures of SopB and SopB-DNA complexes.
  Nucleic Acids Res, 38, 4514-4526.
PDB codes: 3kz5 3mkw 3mky 3mkz
20717979 T.Nagata, E.Niyada, N.Fujimoto, Y.Nagasaki, K.Noto, Y.Miyanoiri, J.Murata, K.Hiratsuka, and M.Katahira (2010).
Solution structures of the trihelix DNA-binding domains of the wild-type and a phosphomimetic mutant of Arabidopsis GT-1: mechanism for an increase in DNA-binding affinity through phosphorylation.
  Proteins, 78, 3033-3047.
PDB codes: 2ebi 2jmw
19309455 A.Chini, S.Fonseca, J.M.Chico, P.Fernández-Calvo, and R.Solano (2009).
The ZIM domain mediates homo- and heteromeric interactions between Arabidopsis JAZ proteins.
  Plant J, 59, 77-87.  
19449889 J.Xu, G.Chen, A.T.De Jong, S.H.Shahravan, and J.A.Shin (2009).
Max-E47, a designed minimalist protein that targets the E-box DNA site in vivo and in vitro.
  J Am Chem Soc, 131, 7839-7848.  
18949049 H.K.Chow, J.Xu, S.H.Shahravan, A.T.De Jong, G.Chen, and J.A.Shin (2008).
Hybrids of the bHLH and bZIP protein motifs display different DNA-binding activities in vivo vs. in vitro.
  PLoS ONE, 3, e3514.  
16260616 D.Skowronska-Krawczyk, L.Matter-Sadzinski, M.Ballivet, and J.M.Matter (2005).
The basic domain of ATH5 mediates neuron-specific promoter activity during retina development.
  Mol Cell Biol, 25, 10029-10039.  
16356863 H.C.Chang, K.Tan, J.Ouyang, E.Parisini, J.H.Liu, Y.Le, X.Wang, E.L.Reinherz, and J.H.Wang (2005).
Structural and mutational analyses of a CD8alphabeta heterodimer and comparison with the CD8alphaalpha homodimer.
  Immunity, 23, 661-671.
PDB code: 2atp
15563456 K.Swales, S.Kakizaki, Y.Yamamoto, K.Inoue, K.Kobayashi, and M.Negishi (2005).
Novel CAR-mediated mechanism for synergistic activation of two distinct elements within the human cytochrome P450 2B6 gene in HepG2 cells.
  J Biol Chem, 280, 3458-3466.  
15121849 A.V.Grinberg, C.D.Hu, and T.K.Kerppola (2004).
Visualization of Myc/Max/Mad family dimers and the competition for dimerization in living cells.
  Mol Cell Biol, 24, 4294-4308.  
15112996 E.C.Turner, C.H.Cureton, C.J.Weston, O.S.Smart, and R.K.Allemann (2004).
Controlling the DNA binding specificity of bHLH proteins through intramolecular interactions.
  Chem Biol, 11, 69-77.  
14968135 G.D.Amoutzias, D.L.Robertson, S.G.Oliver, and E.Bornberg-Bauer (2004).
Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.
  EMBO Rep, 5, 274-279.  
15356290 H.P.Shanahan, M.A.Garcia, S.Jones, and J.M.Thornton (2004).
Identifying DNA-binding proteins using structural motifs and the electrostatic potential.
  Nucleic Acids Res, 32, 4732-4741.  
15084581 M.J.Dubin, P.H.Stokes, E.Y.Sum, R.S.Williams, V.A.Valova, P.J.Robinson, G.J.Lindeman, J.N.Glover, J.E.Visvader, and J.M.Matthews (2004).
Dimerization of CtIP, a BRCA1- and CtBP-interacting protein, is mediated by an N-terminal coiled-coil motif.
  J Biol Chem, 279, 26932-26938.  
14643885 R.J.Kewley, M.L.Whitelaw, and A.Chapman-Smith (2004).
The mammalian basic helix-loop-helix/PAS family of transcriptional regulators.
  Int J Biochem Cell Biol, 36, 189-204.  
12923186 C.I.Rodríguez, N.Gironès, and M.Fresno (2003).
Cha, a basic helix-loop-helix transcription factor involved in the regulation of upstream stimulatory factor activity.
  J Biol Chem, 278, 43135-43145.  
12538578 M.A.Nikiforov, N.Popov, I.Kotenko, M.Henriksson, and M.D.Cole (2003).
The Mad and Myc basic domains are functionally equivalent.
  J Biol Chem, 278, 11094-11099.  
12514181 R.Ciarapica, J.Rosati, G.Cesareni, and S.Nasi (2003).
Molecular recognition in helix-loop-helix and helix-loop-helix-leucine zipper domains. Design of repertoires and selection of high affinity ligands for natural proteins.
  J Biol Chem, 278, 12182-12190.  
12553908 S.K.Nair, and S.K.Burley (2003).
X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors.
  Cell, 112, 193-205.
PDB codes: 1nkp 1nlw
12186881 M.H.Godsey, E.E.Zheleznova Heldwein, and R.G.Brennan (2002).
Structural biology of bacterial multidrug resistance gene regulators.
  J Biol Chem, 277, 40169-40172.  
11891322 T.Berg, S.B.Cohen, J.Desharnais, C.Sonderegger, D.J.Maslyar, J.Goldberg, D.L.Boger, and P.K.Vogt (2002).
Small-molecule antagonists of Myc/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts.
  Proc Natl Acad Sci U S A, 99, 3830-3835.  
11350941 D.Ghosh, T.I.Gerasimova, and V.G.Corces (2001).
Interactions between the Su(Hw) and Mod(mdg4) proteins required for gypsy insulator function.
  EMBO J, 20, 2518-2527.  
11031250 C.Grandori, S.M.Cowley, L.P.James, and R.N.Eisenman (2000).
The Myc/Max/Mad network and the transcriptional control of cell behavior.
  Annu Rev Cell Dev Biol, 16, 653-699.  
10594029 T.Kophengnavong, J.E.Michnowicz, and T.K.Blackwell (2000).
Establishment of distinct MyoD, E2A, and twist DNA binding specificities by different basic region-DNA conformations.
  Mol Cell Biol, 20, 261-272.  
10543451 J.Vervoorts, and B.Lüscher (1999).
DNA binding of Myc/Max/Mad network complexes to oligonucleotides containing two E box elements: c-Myc/Max heterodimers do not bind DNA cooperatively.
  Biol Chem, 380, 1121-1126.  
10026283 K.Nadassy, S.J.Wodak, and J.Janin (1999).
Structural features of protein-nucleic acid recognition sites.
  Biochemistry, 38, 1999-2017.  
9521744 A.G.K-unne, M.Sieber, D.Meierhans, and R.K.Allemann (1998).
Thermodynamics of the DNA binding reaction of transcription factor MASH-1.
  Biochemistry, 37, 4217-4223.  
9634703 A.Párraga, L.Bellsolell, A.R.Ferré-D'Amaré, and S.K.Burley (1998).
Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution.
  Structure, 6, 661-672.
PDB code: 1am9
9519295 S.Tan, and T.J.Richmond (1998).
Eukaryotic transcription factors.
  Curr Opin Struct Biol, 8, 41-48.  
9368002 M.W.Kennedy, L.H.Garside, L.E.Goodrick, L.McDermott, A.Brass, N.C.Price, S.M.Kelly, A.Cooper, and J.E.Bradley (1997).
The Ov20 protein of the parasitic nematode Onchocerca volvulus. A structurally novel class of small helix-rich retinol-binding proteins.
  J Biol Chem, 272, 29442-29448.  
9782776 R.E.Dickerson, and T.K.Chiu (1997).
Helix bending as a factor in protein/DNA recognition.
  Biopolymers, 44, 361-403.  
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.