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PDBsum entry 1mdy

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protein dna_rna Protein-protein interface(s) links
Transcription/DNA PDB id
1mdy
Jmol
Contents
Protein chains
68 a.a. *
62 a.a. *
DNA/RNA
Waters ×25
* Residue conservation analysis
PDB id:
1mdy
Name: Transcription/DNA
Title: Crystal structure of myod bhlh domain bound to dna: perspectives on DNA recognition and implications for transcriptional activation
Structure: DNA (5'- d( Tp Cp Ap Ap Cp Ap Gp Cp Tp Gp Tp Tp Gp A)-3'). Chain: e, f, g, h. Engineered: yes. Protein (myod bhlh domain). Chain: a. Protein (myod bhlh domain). Chain: b, c, d
Source: Synthetic: yes. Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090
Biol. unit: Dimer (from PQS)
Resolution:
2.80Å     R-factor:   0.253     R-free:   0.330
Authors: P.C.M.Ma,M.A.Rould,H.Weintraub,C.O.Pabo
Key ref: P.C.Ma et al. (1994). Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Cell, 77, 451-459. PubMed id: 8181063 DOI: 10.1016/0092-8674(94)90159-7
Date:
09-Jun-94     Release date:   31-Aug-94    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P10085  (MYOD1_MOUSE) -  Myoblast determination protein 1
Seq:
Struc:
318 a.a.
68 a.a.*
Protein chains
Pfam   ArchSchema ?
P10085  (MYOD1_MOUSE) -  Myoblast determination protein 1
Seq:
Struc:
318 a.a.
62 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

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

 

 
DOI no: 10.1016/0092-8674(94)90159-7 Cell 77:451-459 (1994)
PubMed id: 8181063  
 
 
Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation.
P.C.Ma, M.A.Rould, H.Weintraub, C.O.Pabo.
 
  ABSTRACT  
 
The crystal structure of a MyoD basic-helix-loop-helix (bHLH) domain-DNA complex has been solved and refined at 2.8 A resolution. This structure proves that bHLH and bHLH-leucine zipper (bHLH-ZIP) proteins are remarkably similar; it helps us understand subtle differences in binding preferences for these proteins; and it has surprising implications for our understanding of transcription. Specifically, Ala-114 and Thr-115, which are required for positive control in the myogenic proteins, are buried at the protein-DNA interface. These residues are not available for direct protein-protein contacts, but they may determine the conformation of Arg-111. Comparisons with Max suggest that the conformation of this arginine, which is different in the two structures, may play an important role in myogenic transcription.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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Structure of an Ebf1:DNA complex reveals unusual DNA recognition and structural homology with Rel proteins.
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PDB codes: 3mln 3mlo 3mlp
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PDB code: 1wle
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Critical role for lysine 133 in the nuclear ubiquitin-mediated degradation of MyoD.
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An overview of the basic helix-loop-helix proteins.
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Recognition of specific DNA sequences.
  Mol Cell, 8, 937-946.  
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Molecular distinction between specification and differentiation in the myogenic basic helix-loop-helix transcription factor family.
  Mol Cell Biol, 21, 2404-2412.  
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Specific protein-protein interaction between basic helix-loop-helix transcription factors and homeoproteins of the Pitx family.
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The basic helix-loop-helix transcription factor E2-2 is involved in T lymphocyte development.
  Eur J Immunol, 30, 2857-2863.  
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Backbone dynamics of sequence specific recognition and binding by the yeast Pho4 bHLH domain probed by NMR.
  Protein Sci, 9, 2354-2365.  
11071933 K.A.Robinson, J.I.Koepke, M.Kharodawala, and J.M.Lopes (2000).
A network of yeast basic helix-loop-helix interactions.
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SURVEY AND SUMMARY: Saccharomyces cerevisiae basic helix-loop-helix proteins regulate diverse biological processes.
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10725404 K.R.Wollenberg, and W.R.Atchley (2000).
Separation of phylogenetic and functional associations in biological sequences by using the parametric bootstrap.
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10773081 M.Sieber, and R.K.Allemann (2000).
Thermodynamics of DNA binding of MM17, a 'single chain dimer' of transcription factor MASH-1.
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OUT, a novel basic helix-loop-helix transcription factor with an Id-like inhibitory activity.
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11025438 P.L.Puri, and V.Sartorelli (2000).
Regulation of muscle regulatory factors by DNA-binding, interacting proteins, and post-transcriptional modifications.
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Diabetes-associated mutations in a beta-cell transcription factor destabilize an antiparallel "mini-zipper" in a dimerization interface.
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PDB code: 1dt8
10707973 S.E.Goulding, P.zur Lage, and A.P.Jarman (2000).
amos, a proneural gene for Drosophila olfactory sense organs that is regulated by lozenge.
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P/CAF-mediated acetylation regulates the function of the basic helix-loop-helix transcription factor TAL1/SCL.
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Establishment of distinct MyoD, E2A, and twist DNA binding specificities by different basic region-DNA conformations.
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10430036 C.Dezan, D.Meierhans, A.G.Künne, and R.K.Allemann (1999).
Acquisition of myogenic specificity through replacement of one amino acid of MASH-1 and introduction of an additional alpha-helical turn.
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Co-crystal structure of sterol regulatory element binding protein 1a at 2.3 A resolution.
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PDB code: 1am9
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Multiple roles for the MyoD basic region in transmission of transcriptional activation signals and interaction with MEF2.
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DNA-mediated folding and assembly of MyoD-E47 heterodimers.
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Role of the PAS domain in regulation of dimerization and DNA binding specificity of the dioxin receptor.
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Dimerization as a regulatory mechanism in signal transduction.
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Intramolecular regulation of MyoD activation domain conformation and function.
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A helix-turn-helix structure unit in human centromere protein B (CENP-B).
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PDB code: 1bw6
9668115 M.K.Shirra, and U.Hansen (1998).
LSF and NTF-1 share a conserved DNA recognition motif yet require different oligomerization states to form a stable protein-DNA complex.
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Single chain dimers of MASH-1 bind DNA with enhanced affinity.
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Ribosome-inactivating proteins (RIPs) of wild Oregon cucumber (Marah oreganus).
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Structural dissection of the DNA-binding domain of the yeast transcriptional activator GAL4 reveals an alpha-helical region responsible for dimerization.
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A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless.
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Covalently linking BHLH subunits of MASH-1 increases specificity of DNA binding.
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Rtg3p, a basic helix-loop-helix/leucine zipper protein that functions in mitochondrial-induced changes in gene expression, contains independent activation domains.
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A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein.
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High affinity binding of MEF-2C correlates with DNA bending.
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Cdk2-dependent phosphorylation of Id2 modulates activity of E2A-related transcription factors.
  EMBO J, 16, 332-342.  
  9234693 G.Jiménez, and D.Ish-Horowicz (1997).
A chimeric enhancer-of-split transcriptional activator drives neural development and achaete-scute expression.
  Mol Cell Biol, 17, 4355-4362.  
9184233 G.Meroni, A.Reymond, M.Alcalay, G.Borsani, A.Tanigami, R.Tonlorenzi, C.L.Nigro, S.Messali, M.Zollo, D.H.Ledbetter, R.Brent, A.Ballabio, and R.Carrozzo (1997).
Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor.
  EMBO J, 16, 2892-2906.  
9241421 G.Patikoglou, and S.K.Burley (1997).
Eukaryotic transcription factor-DNA complexes.
  Annu Rev Biophys Biomol Struct, 26, 289-325.  
  9343431 G.Poulin, B.Turgeon, and J.Drouin (1997).
NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene.
  Mol Cell Biol, 17, 6673-6682.  
9295343 J.Onions, S.Hermann, and T.Grundström (1997).
Basic helix-loop-helix protein sequences determining differential inhibition by calmodulin and S-100 proteins.
  J Biol Chem, 272, 23930-23937.  
9237561 J.R.Cann (1997).
Models of mobility-shift assay of complexes between dimerizing protein and DNA.
  Electrophoresis, 18, 1092-1097.  
9312029 J.R.Dutton, S.Johns, and B.L.Miller (1997).
StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans.
  EMBO J, 16, 5710-5721.  
9242638 K.Langlands, X.Yin, G.Anand, and E.V.Prochownik (1997).
Differential interactions of Id proteins with basic-helix-loop-helix transcription factors.
  J Biol Chem, 272, 19785-19793.  
9208942 K.Numayama-Tsuruta, A.Kobayashi, K.Sogawa, and Y.Fujii-Kuriyama (1997).
A point mutation responsible for defective function of the aryl-hydrocarbon-receptor nuclear translocator in mutant Hepa-1c1c7 cells.
  Eur J Biochem, 246, 486-495.  
9111058 K.S.Prasad, and S.J.Brandt (1997).
Target-dependent effect of phosphorylation on the DNA binding activity of the TAL1/SCL oncoprotein.
  J Biol Chem, 272, 11457-11462.  
9115440 P.Brownlie, T.Ceska, M.Lamers, C.Romier, G.Stier, H.Teo, and D.Suck (1997).
The crystal structure of an intact human Max-DNA complex: new insights into mechanisms of transcriptional control.
  Structure, 5, 509-520.
PDB code: 1hlo
9782776 R.E.Dickerson, and T.K.Chiu (1997).
Helix bending as a factor in protein/DNA recognition.
  Biopolymers, 44, 361-403.  
  9007990 R.Fairman, R.K.Beran-Steed, and T.M.Handel (1997).
Heteronuclear (1H, 13C, 15N) NMR assignments and secondary structure of the basic region-helix-loop-helix domain of E47.
  Protein Sci, 6, 175-184.  
9061008 R.Maione, and P.Amati (1997).
Interdependence between muscle differentiation and cell-cycle control.
  Biochim Biophys Acta, 1332, M19-M30.  
9184158 S.J.Maleki, C.A.Royer, and B.K.Hurlburt (1997).
MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable.
  Biochemistry, 36, 6762-6767.  
9570136 S.Morwenna, and W.P.Ratcliffe (1997).
Mammalian oxygen sensing and hypoxia inducible factor-1.
  Int J Biochem Cell Biol, 29, 1419-1432.  
9303313 T.Shimizu, A.Toumoto, K.Ihara, M.Shimizu, Y.Kyogoku, N.Ogawa, Y.Oshima, and T.Hakoshima (1997).
Crystal structure of PHO4 bHLH domain-DNA complex: flanking base recognition.
  EMBO J, 16, 4689-4697.
PDB code: 1a0a
9428527 U.Albrecht, Z.S.Sun, G.Eichele, and C.C.Lee (1997).
A differential response of two putative mammalian circadian regulators, mper1 and mper2, to light.
  Cell, 91, 1055-1064.  
9155024 V.R.Stoldt, A.Sonneborn, C.E.Leuker, and J.F.Ernst (1997).
Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi.
  EMBO J, 16, 1982-1991.  
9053397 W.D.Kohn, C.T.Mant, and R.S.Hodges (1997).
Alpha-helical protein assembly motifs.
  J Biol Chem, 272, 2583-2586.  
9207015 W.Gong, M.O'Gara, R.M.Blumenthal, and X.Cheng (1997).
Structure of pvu II DNA-(cytosine N4) methyltransferase, an example of domain permutation and protein fold assignment.
  Nucleic Acids Res, 25, 2702-2715.
PDB code: 1boo
  9343420 Y.Hamamori, H.Y.Wu, V.Sartorelli, and L.Kedes (1997).
The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist.
  Mol Cell Biol, 17, 6563-6573.  
  9032238 Y.Jia, B.Rothermel, J.Thornton, and R.A.Butow (1997).
A basic helix-loop-helix-leucine zipper transcription complex in yeast functions in a signaling pathway from mitochondria to the nucleus.
  Mol Cell Biol, 17, 1110-1117.  
9374477 Y.Takahashi, K.Nakayama, S.Itoh, Y.Fujii-Kuriyama, and T.Kamataki (1997).
Inhibition of the transcription of CYP1A1 gene by the upstream stimulatory factor 1 in rabbits. Competitive binding of USF1 with AhR.Arnt complex.
  J Biol Chem, 272, 30025-30031.  
8898330 B.Connolly, K.Trenholme, and D.F.Smith (1996).
Molecular cloning of a myoD-like gene from the parasitic nematode, Trichinella spiralis.
  Mol Biochem Parasitol, 81, 137-149.  
8631989 B.N.Fukunaga, and O.Hankinson (1996).
Identification of a novel domain in the aryl hydrocarbon receptor required for DNA binding.
  J Biol Chem, 271, 3743-3749.  
8917575 C.T.Chien, C.D.Hsiao, L.Y.Jan, and Y.N.Jan (1996).
Neuronal type information encoded in the basic-helix-loop-helix domain of proneural genes.
  Proc Natl Acad Sci U S A, 93, 13239-13244.  
9000009 D.A.Erlanson, M.Chytil, and G.L.Verdine (1996).
The leucine zipper domain controls the orientation of AP-1 in the NFAT.AP-1.DNA complex.
  Chem Biol, 3, 981-991.  
  9003784 G.Jiménez, S.M.Pinchin, and D.Ish-Horowicz (1996).
In vivo interactions of the Drosophila Hairy and Runt transcriptional repressors with target promoters.
  EMBO J, 15, 7088-7098.  
8940186 H.I.Swanson, and J.Yang (1996).
Mapping the protein/DNA contact sites of the Ah receptor and Ah receptor nuclear translocator.
  J Biol Chem, 271, 31657-31665.  
8940190 J.B.Moss, E.N.Olson, and R.J.Schwartz (1996).
The myogenic regulatory factor MRF4 represses the cardiac alpha-actin promoter through a negative-acting N-terminal protein domain.
  J Biol Chem, 271, 31688-31694.  
8790335 J.D.Molkentin, and E.N.Olson (1996).
Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors.
  Proc Natl Acad Sci U S A, 93, 9366-9373.  
  8668207 J.Huang, T.K.Blackwell, L.Kedes, and H.Weintraub (1996).
Differences between MyoD DNA binding and activation site requirements revealed by functional random sequence selection.
  Mol Cell Biol, 16, 3893-3900.  
  8816435 K.Gradin, J.McGuire, R.H.Wenger, I.Kvietikova, M.L.fhitelaw, R.Toftgård, L.Tora, M.Gassmann, and L.Poellinger (1996).
Functional interference between hypoxia and dioxin signal transduction pathways: competition for recruitment of the Arnt transcription factor.
  Mol Cell Biol, 16, 5221-5231.  
8561893 K.L.Mak, L.C.Longcor, S.E.Johnson, C.Lemercier, R.Q.To, and S.F.Konieczny (1996).
Examination of mammalian basic helix-loop-helix transcription factors using a yeast one-hybrid system.
  DNA Cell Biol, 15, 1-8.  
8939680 K.Yun, and B.Wold (1996).
Skeletal muscle determination and differentiation: story of a core regulatory network and its context.
  Curr Opin Cell Biol, 8, 877-889.  
  8628310 O.Tournay, and R.Benezra (1996).
Transcription of the dominant-negative helix-loop-helix protein Id1 is regulated by a protein complex containing the immediate-early response gene Egr-1.
  Mol Cell Biol, 16, 2418-2430.  
8621566 P.J.Czernik, C.A.Peterson, and B.K.Hurlburt (1996).
Preferential binding of MyoD-E12 versus myogenin-E12 to the murine sarcoma virus enhancer in vitro.
  J Biol Chem, 271, 9141-9149.  
8962069 R.J.McCormick, T.Badalian, and D.E.Fisher (1996).
The leucine zipper may induce electrophoretic mobility anomalies without DNA bending.
  Proc Natl Acad Sci U S A, 93, 14434-14439.  
  8657135 S.E.Johnson, X.Wang, S.Hardy, E.J.Taparowsky, and S.F.Konieczny (1996).
Casein kinase II increases the transcriptional activities of MRF4 and MyoD independently of their direct phosphorylation.
  Mol Cell Biol, 16, 1604-1613.  
8621524 S.G.Bacsi, and O.Hankinson (1996).
Functional characterization of DNA-binding domains of the subunits of the heterodimeric aryl hydrocarbon receptor complex imputing novel and canonical basic helix-loop-helix protein-DNA interactions.
  J Biol Chem, 271, 8843-8850.  
  8918463 S.M.Maira, J.M.Wurtz, and B.Wasylyk (1996).
Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif.
  EMBO J, 15, 5849-5865.  
8900045 W.E.Wright, I.Dac-Korytko, and K.Farmer (1996).
Monoclonal antimyogenin antibodies define epitopes outside the bHLH domain where binding interferes with protein-protein and protein-DNA interactions.
  Dev Genet, 19, 131-138.  
8662987 Z.Mao, and B.Nadal-Ginard (1996).
Functional and physical interactions between mammalian achaete-scute homolog 1 and myocyte enhancer factor 2A.
  J Biol Chem, 271, 14371-14375.  
7775458 C.Antonsson, V.Arulampalam, M.L.Whitelaw, S.Pettersson, and L.Poellinger (1995).
Constitutive function of the basic helix-loop-helix/PAS factor Arnt. Regulation of target promoters via the E box motif.
  J Biol Chem, 270, 13968-13972.  
  8601486 D.A.Barbash, and T.W.Cline (1995).
Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster.
  Genetics, 141, 1451-1471.  
7592839 H.I.Swanson, W.K.Chan, and C.A.Bradfield (1995).
DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins.
  J Biol Chem, 270, 26292-26302.  
  7739539 J.B.Kim, G.D.Spotts, Y.D.Halvorsen, H.M.Shih, T.Ellenberger, H.C.Towle, and B.M.Spiegelman (1995).
Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain.
  Mol Cell Biol, 15, 2582-2588.  
8548800 J.D.Molkentin, B.L.Black, J.F.Martin, and E.N.Olson (1995).
Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins.
  Cell, 83, 1125-1136.  
7568211 J.L.Pomerantz, C.O.Pabo, and P.A.Sharp (1995).
Analysis of homeodomain function by structure-based design of a transcription factor.
  Proc Natl Acad Sci U S A, 92, 9752-9756.  
7582955 M.Okagami, M.Ueno, K.Makino, M.Shimomura, I.Saito, T.Morii, and Y.Sugiura (1995).
Sequence-specific DNA binding by covalently constrained peptide dimers of the basic leucine zipper protein GCN4.
  Bioorg Med Chem, 3, 777-784.  
  7737127 M.Shirakata, and B.M.Paterson (1995).
The E12 inhibitory domain prevents homodimer formation and facilitates selective heterodimerization with the MyoD family of gene regulatory factors.
  EMBO J, 14, 1766-1772.  
8749848 M.Suzuki, and M.Gerstein (1995).
Binding geometry of alpha-helices that recognize DNA.
  Proteins, 23, 525-535.  
7753857 M.Vandromme, J.C.Cavadore, A.Bonnieu, A.Froeschlé, N.Lamb, and A.Fernandez (1995).
Two nuclear localization signals present in the basic-helix 1 domains of MyoD promote its active nuclear translocation and can function independently.
  Proc Natl Acad Sci U S A, 92, 4646-4650.  
7736571 N.Navaratnam, S.Bhattacharya, T.Fujino, D.Patel, A.L.Jarmuz, and J.Scott (1995).
Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site.
  Cell, 81, 187-195.  
7890710 P.Shore, L.Bisset, J.Lakey, J.P.Waltho, R.Virden, and A.D.Sharrocks (1995).
Characterization of the Elk-1 ETS DNA-binding domain.
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  7791788 S.M.Hollenberg, R.Sternglanz, P.F.Cheng, and H.Weintraub (1995).
Identification of a new family of tissue-specific basic helix-loop-helix proteins with a two-hybrid system.
  Mol Cell Biol, 15, 3813-3822.  
7862526 S.Schwank, R.Ebbert, K.Rautenstrauss, E.Schweizer, and H.J.Schüller (1995).
Yeast transcriptional activator INO2 interacts as an Ino2p/Ino4p basic helix-loop-helix heteromeric complex with the inositol/choline-responsive element necessary for expression of phospholipid biosynthetic genes in Saccharomyces cerevisiae.
  Nucleic Acids Res, 23, 230-237.  
  7565669 Y.Kong, S.E.Johnson, E.J.Taparowsky, and S.F.Konieczny (1995).
Ras p21Val inhibits myogenesis without altering the DNA binding or transcriptional activities of the myogenic basic helix-loop-helix factors.
  Mol Cell Biol, 15, 5205-5213.  
7880524 A.B.Lassar, S.X.Skapek, and B.Novitch (1994).
Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal.
  Curr Opin Cell Biol, 6, 788-794.  
7664056 C.Wolberger (1994).
b/HLH without the zip.
  Nat Struct Biol, 1, 413-416.  
7849514 M.E.Buckingham (1994).
Muscle: the regulation of myogenesis.
  Curr Opin Genet Dev, 4, 745-751.  
  7969122 Y.Peleg, and R.L.Metzenberg (1994).
Analysis of the DNA-binding and dimerization activities of Neurospora crassa transcription factor NUC-1.
  Mol Cell Biol, 14, 7816-7826.  
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.