2.3 Å crystal structure of tetanus neurotoxin light chain

TeNT is the causative agent of the neuroparalytic disease tetanus. A key component of TeNT (2+) endopeptidase that targets SNAREs. Recent structural studies of closely related is its light chain, a Zn (2+), 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 angstrom X-ray crystal structure of TeNTLC, 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 thermolysinlike 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.