PDBsum entry: 2vse

Toxin

PDB id: 2vse

Contents

Protein chains

823 a.a.

Ligands

MPD ×3

GOL

Waters ×676

PDB id:

2vse

Name:

Toxin

Title:

Structure and mode of action of a mosquitocidal holotoxin

Structure:

Mosquitocidal toxin. Chain: a, b. Fragment: holotoxin, residues 30-870. Synonym: mtx holotoxin. Engineered: yes

Source:

Lysinibacillus sphaericus. Organism_taxid: 1421. Strain: ssii-1. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.50Å R-factor: 0.194 R-free: 0.234

Authors:

N.Treiber,D.J.Reinert,I.Carpusca,K.Aktories,G.E.Schulz

Key ref:

N.Treiber et al. (2008). Structure and mode of action of a mosquitocidal holotoxin. J Mol Biol, 381, 150-159. PubMed id: 18586267 DOI: 10.1016/j.jmb.2008.05.067

Date:

22-Apr-08 Release date: 08-Jul-08

Protein chains

Q03988  (Q03988_LYSSH) -  Mosquitocidal toxin

Seq: 870 a.a.

Struc: 823 a.a.

DOI no: 10.1016/j.jmb.2008.05.067

J Mol Biol 381:150-159 (2008)

PubMed id: 18586267

Structure and mode of action of a mosquitocidal holotoxin.

N.Treiber, D.J.Reinert, I.Carpusca, K.Aktories, G.E.Schulz.

ABSTRACT

The crystal structure of the full mosquitocidal toxin from Bacillus sphaericus (MTX(holo)) has been determined at 2.5 A resolution by the molecular replacement method. The resulting structure revealed essentially the complete chain consisting of four ricin B-type domains curling around the catalytic domain in a hedgehog-like assembly. As the structure was virtually identical in three different crystal packings, it is probably not affected by packing contacts. The structure of MTX(holo) explains earlier autoinhibition data. An analysis of published complexes comprising ricin B-type lectin domains and sugar molecules shows that the general construction principle applies to all four lectin domains of MTX(holo), indicating 12 putative sugar-binding sites. These sites are sequence-related to those of the cytotoxin pierisin from cabbage butterfly, which are known to bind glycolipids. It seems therefore likely that MTX(holo) also binds glycolipids. The seven contact interfaces between the five domains are predominantly polar and not stronger than common crystal contacts so that in an appropriate environment, the multidomain structure would likely uncurl into a string of single domains. The structure of the isolated catalytic domain plus an extended linker was established earlier in three crystal packings, two of which showed a peculiar association around a 7-fold axis. The catalytic domain of the reported MTX(holo) closely resembles all three published structures, except one with an appreciable deviation of the 40 N-terminal residues. A comparison of all structures suggests a possible scenario for the translocation of the toxin into the cytosol.

Selected figure(s)

Figure 1.
Fig. 1. Stereo view of a ribbon plot of MTX[holo]. The catalytic domain (blue), the linker (residues 265–295, red) and the four RBL domains (cyan, green, yellow and orange) are color-coded and labeled. The missing residues at the ARTT loop (189–192) and at the activation loop (262–270) are bridged by dotted lines. Loop 117–124 is labeled. Residues 30–70 preceding the common chain fold of ADP-ribosylating enzymes are purple. They are not tightly fastened to the catalytic domain.^8 The depicted NAD^+ molecule was modeled for MTX[cali]^8 but also applies for MTX[holo].

Figure 5.
Fig. 5. Functional aspects of MTX[holo]. (a) MTX[holo] shown as an inflated C^α backbone model color-coded for domains, linker and unstable N-terminal residues as in Fig. 1. The putative sugar-binding sites are marked by red balls and labeled. The pseudo-3-fold axes of the RBL domains are shown as black sticks. (b) Suggested heptameric association of the catalytic domains of the multidomain protein MTX[holo] after disassembly into a string of five domains. The RBL domains (spheres of equivalent volume) are depicted as bound to glycolipids of a membrane. The unstable N-terminal residues 30–70 of each heptamer subunit contact the membrane surface.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 381, 150-159) copyright 2008.

Figures were selected by the author.