Cell division proteins

MinE topological specificity domain Download coordinates:  1ev0.pdb (3.1 Mb)    1ev0.pdb.gz (647 K) The molecular mechanism by which cells choose their future division site is poorly understood. In E. coli, correct positioning of the division septum depends on the coordinated action of the MinC, MinD, and MinE proteins. MinC and MinD act in concert to form a global division inhibitor. MinE protects the preferred central division site by localizing to an annular structure at midcell and dissociating the MinCD complex in the vicinity of this ring. Topological specificity (i.e., the ability to counteract MinCD only at midcell) is conferred by a structurally autonomous topological specificity domain (TSD) that is also responsible for midcell localization of MinE. MinE TSD forms a novel homodimeric alpha-beta sandwich; the figure shows one monomer in blue and the other in gold. Structure-directed mutagenesis has enabled us to identify a site on the surface of MinE that is critical for its topological specificity function. Reference: King et al. (2000) Nature Structural Biology 7, 1013-1017.

Eukaryotic transcription factors

c-Jun leucine zipper Download coordinates:  1jun.pdb (820 K)    1jun.pdb.gz (173 K) c-Jun belongs to the bZIP family of eukaryotic transcription factors. In order to transactivate target genes it must either homodimerize or heterodimerize with c-Fos via its leucine zipper (LZ) domain. The c-Jun LZ homodimer is a classical coiled coil in which extended helices from each monomer wrap around one another with a left-handed superhelical twist. The supercoiling is obvious in the adjacent view down the long axis of the dimer. The hydrophobic dimer interface is composed of alternating “rungs” of leucine residues (shown in yellow). Reference: Junius et al. (1996) Journal of Biological Chemistry 271, 13663-13667.

GATA N-terminal zinc finger Download coordinates:  1gnf.pdb (1684 K)    1gnf.pdb.gz (352 K) Although zinc fingers (ZnFs) are generally regarded as DNA-binding motifs, several recent reports have implicated particular ZnFs in mediating protein-protein interactions. The N-terminal ZnF of GATA-1 (NF) is one such finger; it interacts with various proteins, including the recently discovered transcriptional cofactor FOG. NF is a C4-type zinc finger in which the single Zn atom (shown in yellow) is coordinated by four cysteine residues (shown in red). The structure was solved in collaboration with the Mackay lab. Reference: Kowalski et al. (1999) Journal of Biomolecular NMR 13, 249-261.

Toxins

Delta-atracotoxin-Hv1a (versutoxin) Download coordinates:  1vtx.pdb (1130 K)    1vtx.pdb.gz (230 K) Delta-atracotoxin is the lethal component in the venom of Australian funnel-web spiders. It contains four intramolecular disulfide bonds. The toxin produces potentially fatal neurotoxic symptoms in primates by slowing the inactivation of voltage-gated sodium channels. The toxin is unusual in that it binds to both insect and vertebrate voltage-gated sodium channels at picomolar concentrations. Reference: Fletcher et al. (1997) Structure 5, 1525-1535.

J-atracotoxin-Hv1c Download coordinates:  1dl0.pdb (805 K)    1dl0.pdb.gz (169 K) J-atracotoxin-Hv1c is a 37-residue insecticidal neurotoxin isolated from the venom of the Australian funnel-web spider. It has no sequence homologs. The peptide contains four intramolecular disulfide bonds (shown in red), including an extremely rare vicinal disulfide bridge that is essential for insecticidal activity. The molecular target of this toxin is currently unknown, but it displays no vertebrate toxicity. Reference: Wang et al. (2000) Nature Structural Biology 7, 505-513.

Omega-atracotoxin-Hv1a Download coordinates:  1axh.pdb (876 K)    1axh.pdb.gz (183 K) Omega-atracotoxin-Hv1a is a 37-residue insecticidal neurotoxin isolated from the venom of the Australian funnel-web spider. The toxin contains three intramolecular disulfide bonds (shown in red) that form a classical cystine knot motif. The toxin is a promising biopesticide lead by virtue of its ability to specifically antagonise insect, but not vertebrate, voltage-gated calcium channels. The toxin has no sequence or structural homologs. A "Hairpinless" mutant of the toxin (see below) is biologically inactive. Reference: Fletcher et al. (1997) Nature Structural Biology 4, 559-565.

Omega-atracotoxin-Hv2a Download coordinates:  1g9p.pdb (876 K)    1g9p.pdb.gz (183 K) Omega-atracotoxin-Hv2a appears to be the most potent and specific blocker of insect calcium channels discovered to date. It is a 45-residue insecticidal neurotoxin isolated from the venom of the Australian funnel-web spider. The toxin contains three intramolecular disulfide bonds (shown in red) that form a cystine knot motif. The C-terminal 13 residues (not shown) are highly lipophilic, structurally disordered in solution, and essential for insecticidal activity. The toxin inhibits insect voltage-gated calcium channels with an EC50 of about 130 picomolar, but it is more than 10,000-fold less effective on vertebrate calcium channels. Reference: Wang et al. (2001) Journal of Biological Chemistry 276, 40306-40312

Defensin-like peptide 1 (DLP-1) Download coordinates:  1b8w.pdb (1100 K)    1b8w.pdb.gz (229 K) Defensin-like peptide 1 (DLP-1) is one of three homologous toxins isolated from the venomous hind-leg spur of the male platypus. It is a 42-residue polypeptide with three intramolecular disulfide bonds. DLP-1 is a structural, but not functional, homologue of bovine ß-defensin-12, an antimicrobial peptide, and ShI, a sodium-channel neurotoxin. This structure was determined in collaboration with the Kuchel lab. Reference: Torres et al. (1999) Biochemical Journal 341, 785-794.

Gurmarin Download coordinates:  1c4e.pdb (940 K)    1c4e.pdb.gz (194 K) Gurmarin is a 35-residue polypeptide isolated from the leaves of the Asclepiad vine Gymnema sylvestre. Gurmarin suppresses the response of rat chorda tympani to sweet-tastants such as glucose, sucrose, glycine, and saccharine without affecting responses to salty, sour, and bitter stimuli. The three-dimensional fold of gurmarin is remarkably similar to that of delta-atracotoxin, which raises the possibility that it antagonises a downstream ion channel involved in sweet-taste transduction. The three disulfide bonds are shown in red. Reference: Fletcher et al. (1999) European Journal of Biochemistry 264, 525-533.

“Hairpinless” Download coordinates:  1hvw.pdb (544 K)    1hvw.pdb.gz (88 K) “Hairpinless” is an engineered 25-residue variant of omega-atracotoxin-Hv1a in which the ß-hairpin that protrudes from the disulphide core of the toxin (see stereo image of omega-atracotoxin-Hv1a above) has been excised without affecting the residual fold. The mutant peptide contains the three intramolecular disulfide bonds found in the native toxin. Reference: Tedford et al. (2001) Journal of Biological Chemistry 276, 26568-26576.