Lecture
L(SB)2 Seminar: Lymphostatin: Structure of a non-toxic Toxin
- Date
- Thursday 20 March 2025
- Time
- Location
-
Gorlaeus Building
Einsteinweg 55
2333 CC Leiden - Room
- BE.0.18
Abstract
Enteropathogenic and Enterohaemorrhagic Escherichia coli are enteric pathogens, and human infections can be life-threatening. Lymphostatin is a virulence factor of these bacteria and inhibits mitogen-activated proliferation of lymphocytes without being cell toxic or necrotic. The inhibition of proliferation depends on an N-terminal glycosyltransferase and a central cysteine protease motif, which are often found together in AB-toxins.
We have determined the structure of Lymphostatin at different pH-values using electron cryo microscopy and image processing. We found three conformational states that differ by large scale domain rearrangements. In all three conformations, the active sites of the glycosyltransferase domain and the protease domain are inaccessible. In addition to these domains, we discovered another glycosyltransferase domain and an ADP-ribosyltransferase (ART) domain. Both domains lack the signature motifs for catalytic activity and are most likely non-functional. We think that all three conformations of Lymphostatin represent inactive forms, which require additional host factors for activation.