Crystal structure of group A Streptococcus Mac-1: Insight into dimer-mediated specificity for recognition of human IgG

Johnson Agniswamy, Michal J. Nagiec, Mengyao Liu, Peter Schuck, James M. Musser, Peter D. Sun

Research output: Contribution to journalArticle

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)225-235
Number of pages11
JournalStructure
Volume14
Issue number2
DOIs
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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