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Structural biology of the alternative pathway convertase
Author(s) -
Xu Yuanyuan,
Narayana Sthanam V. L.,
Volanakis John E.
Publication year - 2001
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2001.1800111.x
Subject(s) - zymogen , alternative complement pathway , c3 convertase , proteases , biochemistry , serine protease , complement system , enzyme , serine , subtilisin , protease , biology , protein structure , active site , chemistry , microbiology and biotechnology , immune system , genetics
Summary: Complement convertases are bimolecular complexes expressing protease activity only against C3 and C5. Their action is necessary for production of the biological activities of the complement system. Formation of these complexes proceeds through sequential protein–protein interactions and proteolytic cleavages of high specificity. Recent structural, mutational and functional data on factors D and B have significantly enhanced our understanding of the assembly, action, and regulation of the alternative pathway convertase. These processes were shown to depend critically on conformational changes, only some of which are reversible. The need for such changes is dictated by the zymogen‐like configurations of the active centers of these unique serine proteases. The structural determinants of some of these changes have been defined from structural and mutational analyses of the two enzymes. Transition of factor D from the zymogen‐like to the catalytically active conformation is completely reversible, while the active conformation of the catalytic center of the Bb fragment of factor B is irreversibly attenuated to a great extent on dissociation of the convertase complex. Both mechanisms contribute to the regulation of the proteolytic activity of these enzymes. Additional studies are necessary for a complete description of the elegant mechanisms mediating these processes. The original work discussed was supported in part by USPHS grants AR44505 (JEV) and AI39818 (SVLN).