3V0C

4.3 angstrom crystal structure of an inactive BoNT/A (E224Q/R363A/Y366F)

Summary for 3V0C

• Entry DOI: 10.2210/pdb3v0c/pdb
• Descriptor: BoNT/A, ZINC ION (2 entities in total)
• Functional Keywords: botulinum neurotoxin, toxin, neurotoxin associated protein, progenitor toxin complex, vhh bound interlocked complex, ntnha
• Biological source: Clostridium botulinum
• Total number of polymer chains: 1
• Total formula weight: 151264.13

Authors

Gu, S.,Rumpel, S.,Zhou, J.,Strotmeier, J.,Bigalke, H.,Perry, K.,Shoemaker, C.B.,Rummel, A.,Jin, R. (deposition date: 2011-12-07, release date: 2012-03-14, Last modification date: 2024-10-16)

Primary citation

Gu, S.,Rumpel, S.,Zhou, J.,Strotmeier, J.,Bigalke, H.,Perry, K.,Shoemaker, C.B.,Rummel, A.,Jin, R.
Botulinum neurotoxin is shielded by NTNHA in an interlocked complex.
Science, 335:977-981, 2012

PubMed Abstract: Botulinum neurotoxins (BoNTs) are highly poisonous substances that are also effective medicines. Accidental BoNT poisoning often occurs through ingestion of Clostridium botulinum-contaminated food. Here, we present the crystal structure of a BoNT in complex with a clostridial nontoxic nonhemagglutinin (NTNHA) protein at 2.7 angstroms. Biochemical and functional studies show that NTNHA provides large and multivalent binding interfaces to protect BoNT from gastrointestinal degradation. Moreover, the structure highlights key residues in BoNT that regulate complex assembly in a pH-dependent manner. Collectively, our findings define the molecular mechanisms by which NTNHA shields BoNT in the hostile gastrointestinal environment and releases it upon entry into the circulation. These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.

PubMed: 22363010
DOI: 10.1126/science.1214270

Experimental method

X-RAY DIFFRACTION (4.3 Å)