Crystal structure of botulinum neurotoxin type G light chain: serotype divergence in substrate recognition.
The seven serotypes (A-G) of botulinum neurotoxins (BoNTs) block neurotransmitter release through their specific proteolysis of one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) complex. BoNTs have stringent substrate specificities that are unique for metalloprotease in that they require exceptionally long substrates (1). To understand the molecular reasons for the unique specificities of the BoNTs, we determined the crystal structure of the catalytic light chain (LC) of Clostridium botulinum neurotoxin type G (BoNT/G-LC) at 2.35 A resolution. The structure of BoNT/G-LC reveals a C-terminal beta-sheet that is critical for LC oligomerization and is unlike that seen in the other LC structures. Its structural comparison with thermolysin and the available pool of LC structures reveals important serotype differences that are likely to be involved in substrate recognition of the P1' residue. In addition, structural and sequence analyses have identified a potential exosite of BoNT/G-LC that recognizes a SNARE recognition motif of VAMP.
Arndt
Joseph W
JW
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Yu
Wayne
W
Bi
Fay
F
Stevens
Raymond C
RC
D020816:Amino Acid Motifs; D001665:Binding Sites; D001905:Botulinum Toxins / Q000737:chemistry* / Q000378:metabolism; D003014:Clostridium botulinum / Q000737:chemistry* / Q000145:classification* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D008565:Membrane Proteins / Q000737:chemistry; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D012703:Serotyping; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins / Q000737:chemistry
D008565:Membrane Proteins; D021122:Protein Subunits; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; C488535:botulinum toxin type G; D001905:Botulinum Toxins