Crystal and Solution Structures of a Superantigen from Yersinia pseudotuberculosis Reveal a Jelly-Roll Fold

Abstract

Superantigens are a class of microbial proteins with the ability to excessively activate T cells by binding to the T cell receptor. The staphylococcal and streptococcal superantigens are closely related in structure and possess an N-terminal domain that resembles an OB fold and a C-terminal domain similar to a beta-grasp fold. Yersinia pseudotuberculosis produces superantigens, YPMa, YPMb, and YPMc, which have no significant amino acid similarity to other proteins. We have determined the crystal and solution structures of YPMa, which show that the protein has a jelly-roll fold. The closest structural neighbors to YPMa are viral capsid proteins and members of the tumor necrosis factor superfamily. In the crystal structure, YPMa packs as a trimer, another feature shared with viral capsid proteins and TNF superfamily proteins. However, in solution YPMa behaves as a monomer, and any functional relevance of the trimer observed in the crystals is yet to be established.

The Forgotten: Identification and Functional Characterization of MHC Class II Molecules H2-Eb2 and RT1-Db2

“…Even speculation about a possible binding mode of YPM to MHC class II and its interaction with TCR is nearly impossible, given that results from YPM mutagenesis and experiments with YPM-derived peptides did not allow the identification of YPM surface regions especially critical for YPM-mediated T cell activation (31). Indeed, despite the fact that YPM has a slight structural similarity to the TNF family and some virus capsid proteins (42), it represents its own conserved domain superfamily, as indicated by a recent search of the National Center for Biotechnology Information's Conserved Domain Database (29) (result from BLAST search September 2015).…”

Mutagenesis, biochemical, and biophysical characterization of Mycoplasma arthritidis-derived mitogen

“…This fold is entirely different from that of the pyrogenic SAgs. Recently, the crystal and solution structures of another bacterial SAg, Yersinia pseudotuberculosis mitogen (YPM), were determined (Donadini et al, 2004). YPM has a single domain composed nearly entirely of β-sheet, showing a jelly-roll-like feature.…”

Superantigenic Yersinia pseudotuberculosis Induces the Expression of Granzymes and Perforin by CD4+T Cells

“…First, YPM does not display any genetic or structural homology with the streptococcal and staphylococcal SAgs (3,16,33). Second, ypm's genetic association with the dif recombination motif is not found in the genomes of other SAg-producing bacterial species (12).…”

“…This suggests horizontal acquisition of the ypm gene by Y. pseudotuberculosis. In contrast to Gram-positive SAgs, the YPM crystal structure has revealed a trimeric structure with homology to viral capsid proteins and members of the TNF family (16).…”