5U75

The structure of Staphylococcal Enterotoxin-like X (SElX), a Unique Superantigen

Summary for 5U75

• Entry DOI: 10.2210/pdb5u75/pdb
• Related PRD ID: PRD_900122
• Descriptor: Enterotoxin-like toxin X, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-[alpha-L-fucopyranose-(1-3)]2-acetamido-2-deoxy-alpha-D-glucopyranose (3 entities in total)
• Functional Keywords: staphylococcal superantigen, sialyl lewis x, immune evasion molecule, toxin
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 1
• Total formula weight: 20239.57

Authors

Ting, Y.T.,Young, P.G.,Langley, R.J.,Baker, H.,Fraser, J.D. (deposition date: 2016-12-11, release date: 2017-08-02, Last modification date: 2023-10-04)

Primary citation

Langley, R.J.,Ting, Y.T.,Clow, F.,Young, P.G.,Radcliff, F.J.,Choi, J.M.,Sequeira, R.P.,Holtfreter, S.,Baker, H.,Fraser, J.D.
Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors.
PLoS Pathog., 13:e1006549-e1006549, 2017

PubMed Abstract: Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors. Two major families of which are the staphylococcal superantigens (SAgs) and the Staphylococcal Superantigen-Like (SSL) exoproteins. The former are immunomodulatory toxins that induce a Vβ-specific activation of T cells, while the latter are immune evasion molecules that interfere with a wide range of innate immune defences. The superantigenic properties of Staphylococcal enterotoxin-like X (SElX) have recently been established. We now reveal that SElX also possesses functional characteristics of the SSLs. A region of SElX displays high homology to the sialyl-lactosamine (sLacNac)-specific binding site present in a sub-family of SSLs. By analysing the interaction of SElX with sLacNac-containing glycans we show that SElX has an equivalent specificity and host cell binding range to the SSLs. Mutation of key amino acids in this conserved region affects the ability of SElX to bind to cells of myeloid origin and significantly reduces its ability to protect S. aureus from destruction in a whole blood killing (WBK) assay. Like the SSLs, SElX is up-regulated early during infection and is under the control of the S. aureus exotoxin expression (Sae) two component gene regulatory system. Additionally, the structure of SElX in complex with the sLacNac-containing tetrasaccharide sialyl Lewis X (sLeX) reveals that SElX is a unique single-domain SAg. In summary, SElX is an 'SSL-like' SAg.

PubMed: 28880913
DOI: 10.1371/journal.ppat.1006549

Experimental method

X-RAY DIFFRACTION (1.66 Å)