Molecular docking of superantigens with class II major histocompatibility complex proteins.
The molecular recognition of two superantigens with class II major histocompatibility complex molecules was simulated by using protein-protein docking. Superantigens studied were staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSST-1) in their crystallographic assemblies with HLA-DR1. Rigid-body docking was performed sampling configurational space of the interfacial surfaces by employing a strategy of partitioning the contact regions on HLA-DR1 into separate molecular recognition units. Scoring of docked conformations was based on an electrostatic continuum model evaluated with the finite-difference Poisson-Boltzmann method. Estimates of nonpolar contributions were derived from the buried molecular surface areas. We found for both superantigens that docking the HLA-DR1 surface complementary with the SEB and TSST-1 contact regions containing a homologous hydrophobic surface loop provided sufficient recognition for the reconstitution of native-like conformers exhibiting the highest-scoring free energies. For the SEB complex, the calculations were successful in reproducing the total association free energy. A comparison of the free-energy determinants of the conserved hydrophobic contact residue indicates functional similarity between the two proteins for this interface. Though both superantigens share a common global association mode, differences in binding topology distinguish the conformational specificities underlying recognition.
Department of Cell Biology and Biochemistry, USAMRIID, Frederick, Maryland, USA.
M A
MA
Olson
L
L
Cuff
D000465:Algorithms; D001427:Bacterial Toxins; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D016012:Poisson Distribution; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus; D055672:Static Electricity; D018089:Superantigens / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
D001427:Bacterial Toxins; D004768:Enterotoxins; D015798:HLA-DR1 Antigen; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal