2IJ0

Structural basis of T cell specificity and activation by the bacterial superantigen toxic shock syndrome toxin-1

Summary for 2IJ0

• Entry DOI: 10.2210/pdb2ij0/pdb
• Descriptor: Toxic shock syndrome toxin-1, penultimate affinity-matured variant of hVbeta 2.1, D10 (3 entities in total)
• Functional Keywords: superantigen, protein-protein interaction, protein binding
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 4
• Total formula weight: 69808.48

Authors

Moza, B.,Varma, A.K.,Buonpane, R.A.,Zhu, P.,Herfst, C.A.,Nicholson, M.J.,Wilbuer, A.K.,Nulifer, S.,Wucherpfenning, K.W.,McCormick, J.K.,Kranz, D.M.,Sundberg, E.J. (deposition date: 2006-09-28, release date: 2007-02-20, Last modification date: 2011-07-13)

Primary citation

Moza, B.,Varma, A.K.,Buonpane, R.A.,Zhu, P.,Herfst, C.A.,Nicholson, M.J.,Wilbuer, A.K.,Seth, N.P.,Wucherpfennig, K.W.,McCormick, J.K.,Kranz, D.M.,Sundberg, E.J.
Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1.
Embo J., 26:1187-1197, 2007

PubMed Abstract: Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor beta chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity.

PubMed: 17268555
DOI: 10.1038/sj.emboj.7601531

Experimental method

X-RAY DIFFRACTION (2.25 Å)