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Structural basis for abrogated binding between staphylococcal enterotoxin A superantigen vaccine and MHC‐IIα
Author(s) -
Krupka Heike I.,
Segelke Brent W.,
Ulrich Robert G.,
Ringhofer Sabine,
Knapp Mark,
Rupp Bernhard
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.39702
Subject(s) - superantigen , enterotoxin , major histocompatibility complex , biology , mutant , mhc class ii , microbiology and biotechnology , chemistry , antigen , genetics , immune system , t cell , escherichia coli , gene
Staphylococcal enterotoxins (SEs) are superantigenic protein toxins responsible for a number of life‐threatening diseases. The X‐ray structure of a staphylococcal enterotoxin A (SEA) triple‐mutant (L48R, D70R, and Y92A) vaccine reveals a cascade of structural rearrangements located in three loop regions essential for binding the α subunit of major histocompatibility complex class II (MHC‐II) molecules. A comparison of hypothetical model complexes between SEA and the SEA triple mutant with MHC‐II HLA‐DR1 clearly shows disruption of key ionic and hydrophobic interactions necessary for forming the complex. Extensive dislocation of the disulfide loop in particular interferes with MHC‐IIα binding. The triple‐mutant structure provides new insights into the loss of superantigenicity and toxicity of an engineered superantigen and provides a basis for further design of enterotoxin vaccines.