The zinc-dependent major histocompatibility complex class II binding site of streptococcal pyrogenic exotoxin C is critical for maximal superantigen function and toxic activity.
The cocrystal structure of streptococcal pyrogenic exotoxin C (SPE C) with HLA-DR2a (DRA*0101,DRB5*0101) revealed a zinc-dependent interaction site through residues 167, 201, and 203 on SPE C and residue 81 on the beta-chain of HLA-DR2a (DRA*0101,DRB5*0101). Mutation of these SPE C residues resulted in dramatically reduced biological activities. Thus, the zinc-dependent major histocompatibility complex II binding site is critical for maximal biological function of SPE C.
Tripp
Timothy J
TJ
Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
McCormick
John K
JK
Webb
Jennifer M
JM
Schlievert
Patrick M
PM
D000818:Animals; D001426:Bacterial Proteins; D001665:Binding Sites; D005098:Exotoxins / Q000737:chemistry / Q000633:toxicity*; D015802:HLA-DR2 Antigen / Q000378:metabolism*; D008565:Membrane Proteins; D011817:Rabbits; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000737:chemistry / Q000633:toxicity*; D015032:Zinc / Q000494:pharmacology*
D001426:Bacterial Proteins; D005098:Exotoxins; D015802:HLA-DR2 Antigen; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; D015032:Zinc