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.
