3PME

Crystal structure of the receptor binding domain of botulinum neurotoxin C/D mosaic serotype

Summary for 3PME

• Entry DOI: 10.2210/pdb3pme/pdb
• Descriptor: Type C neurotoxin, SULFATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: structural genomics, seattle structural genomics center for infectious disease, ssgcid, botulinum neurotoxin, receptor binding domain, ganglioside, phosphatidylethanolamine, mosaic serotype, toxin
• Biological source: Clostridium botulinum
• Total number of polymer chains: 1
• Total formula weight: 49401.57

Authors

Zhang, Y.,Buchko, G.W.,Qin, L.,Robinson, H.,Varnum, S.M.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2010-11-16, release date: 2010-12-15, Last modification date: 2011-07-13)

Primary citation

Zhang, Y.,Buchko, G.W.,Qin, L.,Robinson, H.,Varnum, S.M.
Crystal structure of the receptor binding domain of the botulinum C-D mosaic neurotoxin reveals potential roles of lysines 1118 and 1136 in membrane interactions.
Biochem.Biophys.Res.Commun., 404:407-412, 2011

PubMed Abstract: The botulinum neurotoxins (BoNTs) produced by different strains of the bacterium Clostridium botulinum are responsible for the disease botulism and include a group of immunologically distinct serotypes (A, B, E, and F) that are considered to be the most lethal natural proteins known for humans. Two BoNT serotypes, C and D, while rarely associated with human infection, are responsible for deadly botulism outbreaks afflicting animals. Also associated with animal infections is the BoNT C-D mosaic protein (BoNT/CD), a BoNT subtype that is essentially a hybrid of the BoNT/C (∼two-third) and BoNT/D (∼one-third) serotypes. While the amino acid sequence of the heavy chain receptor binding (HCR) domain of BoNT/CD (BoNT/CD-HCR) is very similar to the corresponding amino acid sequence of BoNT/D, BoNT/CD-HCR binds synaptosome membranes better than BoNT/D-HCR. To obtain structural insights for the different membrane binding properties, the crystal structure of BoNT/CD-HCR (S867-E1280) was determined at 1.56 Å resolution and compared to previously reported structures for BoNT/D-HCR. Overall, the BoNT/CD-HCR structure is similar to the two sub-domain organization observed for other BoNT HCRs: an N-terminal jellyroll barrel motif and a C-terminal β-trefoil fold. Comparison of the structure of BoNT/CD-HCR with BoNT/D-HCR indicates that K1118 has a similar structural role as the equivalent residue, E1114, in BoNT/D-HCR, while K1136 has a structurally different role than the equivalent residue, G1132, in BoNT/D-HCR. Lysine-1118 forms a salt bridge with E1247 and may enhance membrane interactions by stabilizing the putative membrane binding loop (K1240-N1248). Lysine-1136 is observed on the surface of the protein. A sulfate ion bound to K1136 may mimic a natural interaction with the negatively changed phospholipid membrane surface. Liposome-binding experiments demonstrate that BoNT/CD-HCR binds phosphatidylethanolamine liposomes more tightly than BoNT/D-HCR.

PubMed: 21130733
DOI: 10.1016/j.bbrc.2010.11.134

Experimental method

X-RAY DIFFRACTION (1.56 Å)