2AVW | pdb_00002avw

Crystal structure of group a streptococcus mac-1: insight into dimer-mediated specificity for recognition of human IgG.

(2006) Structure 14: 225-235

• PubMed: 16472742 Search on PubMed
• DOI: https://doi.org/10.1016/j.str.2005.10.012
• Primary Citation of Related Structures:  
  2AU1, 2AVW


• PubMed Abstract: 
  

  Group A Streptococcus secretes cysteine proteases named Mac-1 and Mac-2 that mediate host immune evasion by targeting both IgG and Fc receptors. Here, we report the crystal structures of Mac-1 and its catalytically inactive C94A mutant in two different crystal forms. Despite the lack of sequence homology, Mac-1 adopts the canonical papain fold. Alanine mutations at the active site confirmed the critical residues involved in a papain-like catalytic mechanism. Mac-1 forms a symmetric dimer in both crystal forms and displays the unique dimer interface among papain superfamily members. Mutations at the dimer interface resulted in a significant reduction in IgG binding and catalysis, suggesting that the dimer contributes to both IgG specificity and enzyme cooperativity. A tunnel observed at the dimer interface constitutes a target for designing potential Mac-1-specific antimicrobial agents. The structures also offer insight into the functional difference between Mac-1 and Mac-2.

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Organizational Affiliation: 
• Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12441 Parklawn Drive, Rockville, Maryland 20852, USA.