2.3 A crystal structure of tetanus neurotoxin light chain.
TeNT is the causative agent of the neuroparalytic disease tetanus. A key component of TeNT is its light chain, a Zn(2+) endopeptidase that targets SNAREs. Recent structural studies of closely related BoNT endopeptidases indicate that substrate-binding exosites remote from a conserved active site are the primary determinants of substrate specificity. Here we report the 2.3 A X-ray crystal structure of TeNT-LC, determined by combined molecular replacement and MAD phasing. As expected, the overall structure of TeNT-LC is similar to the other known CNT light chain structures, including a conserved thermolysin-like core inserted between structurally distinct amino- and carboxy-terminal regions. Differences between TeNT-LC and the other CNT light chains are mainly limited to surface features such as unique electrostatic potential profiles. An analysis of surface residue conservation reveals a pattern of relatively high variability matching the path of substrate binding around BoNT/A, possibly serving to accommodate the variations in different SNARE targets of the CNT group.
Breidenbach
Mark A
MA
Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA.
Brunger
Axel T
AT
D000595:Amino Acid Sequence; D003460:Crystallization; D018360:Crystallography, X-Ray; D008666:Metalloendopeptidases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D050600:SNARE Proteins; D055672:Static Electricity; D013379:Substrate Specificity; D013744:Tetanus Toxin / Q000737:chemistry* / Q000378:metabolism; D013820:Thermolysin / Q000737:chemistry; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism
D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D050600:SNARE Proteins; D013744:Tetanus Toxin; D033921:Vesicular Transport Proteins; D008666:Metalloendopeptidases; C093556:zinc-endopeptidase, tetanus neurotoxin; D013820:Thermolysin