The crystal structure of staphylococcal enterotoxin H: Implications for binding properties to MHC class II and TcR molecules

The X-ray structure of the superantigen staphylococcal enterotoxin H (SEH) has been determined at 1.69 Angstrom resolution. In this paper we present t wo structures of zinc-free SEH (apoSEH) and one zinc-loaded form of SEH (Zn SEH). SEH exhibits the conventional superantigen (SAg) fold with two charac teristic domains. In ZnSEH one zinc ion per SEH molecule is bound to the C- terminal beta-sheet in the region implicated for major histocompatibility c omplex class II (MHC class II) binding in SEA, SED and SEE. Surprisingly, t he zinc ion has only two ligating amino acid residues His206 and Asp208. Th e other Ligands to the zinc ion are two water molecules. An extensive packi ng interaction between two symmetry-related molecules in the crystal, 834 A ngstrom(2)/molecule, forms a cavity that buries the zinc ions of the molecu les. This dimer-like interaction is found in two crystal forms. Nevertheles s, zinc-dependent dimerisation is not observed in solution, as seen in the case of SED. A unique feature of SEH as compared to other staphylococcal en terotoxins is a large negatively charged surface close to the Zn2+ site. Th e interaction of SEH with MHC class II is the strongest known among the sta phylococcal enterotoxins. However, SEH seems to lack a SEE-like MHC class I I binding site, since the side-chain properties of structurally equivalent amino acid residues in SEH and those in SEE-binding MHC class II differ dra matically. There is also a structural flexibility between the domains of SE H. The domains of two apoSEH structures are related by a 5 degrees rotation leading to at most 3 Angstrom difference in C-alpha positions. Since the T -cell receptor probably interacts with both domains, SEH by this rotation m ay modulate its binding to different TcR V beta-chains. (C) 2000 Academic P ress.