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Structure and function of complement C5 convertase enzymes.

M K Pangburn1, N Rawal

  • 1Department of Biochemistry, University of Texas Health Science Center, Tyler 75708, USA. michael.pangbum@uthct.edu

Biochemical Society Transactions
|November 21, 2002
PubMed
Summary
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Complement C5 convertases gain C5 specificity after cleaving C3. C3b deposition on these enzymes shifts their substrate preference from C3 to C5, initiating the membrane attack complex.

Area of Science:

  • Immunology
  • Biochemistry
  • Molecular Biology

Background:

  • The complement system is crucial for innate and adaptive immunity.
  • C5 convertases are key enzymes in the complement cascade, initiating the membrane attack complex.
  • These enzymes exhibit unique substrate specificity regulation.

Purpose of the Study:

  • To elucidate the mechanism by which C5 convertases acquire specificity for C5.
  • To investigate the role of C3 cleavage products in regulating C5 convertase activity.
  • To understand the switch in enzymatic activity from C3 to C5.

Main Methods:

  • Biochemical assays to measure enzyme kinetics (Km and Vmax).
  • Analysis of protein-protein interactions and complex formation.

Related Experiment Videos

  • Studies on the effect of C3b deposition on enzyme activity and specificity.
  • Main Results:

    • C5 convertases (classical/lectin: C4b2a; alternative: C3bBb) are intrinsically unstable.
    • Newly assembled enzymes preferentially cleave C3, with low affinity for C5.
    • Covalent deposition of C3b onto the enzyme significantly enhances C5 binding affinity (>1000-fold), switching specificity.

    Conclusions:

    • Enzymatic specificity for C5 is acquired post-cleavage of C3.
    • C3b deposition acts as a critical regulatory mechanism, tuning C5 convertase activity.
    • This substrate-induced specificity switch ensures efficient initiation of the membrane attack complex at microbial surfaces.