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The Alternative Pathway C3/C5 Convertase: Chemical Basis of Factor B Activation^1,2,

From the Department of Molecular Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037

Abstract

The structural basis of activation of the alternative pathway C3 convertase was explored. For this purpose a modified isolation procedure of the activating enzyme, Factor D, was elaborated. The procedure affords a 70,000-fold purification of the enzyme with a 20% yield. A simple assay was designed for the quantitation of both Factor D and Factor B activity. On the basis of activity measurements and amino acid analysis, Factor D concentration in plasma was estimated to be 1 µg/ml. Highly purified Factor D was used to activate Factor B in the presence of C3b and Mg⁺⁺. The resulting fragments, Ba and Bb, were characterized with respect to their circular dichroism spectra, amino acid compositions, reactive sulfhydryl groups, and partial amino- and carboxy-terminal sequences. The results indicate that the BA fragment constitutes the amino-terminal region and the Bb fragment the carboxy-terminal region of Factor B. The bond in Factor B that is cleaved by Factor D is proposed to be an arginyl-lysine bond.

Footnotes

¹ This is publication Number 1739 from the Research Institute of Scripps Clinic. This investigation was supported by United States Public Health Service Grants AI 07007, AI 14099, HL 16411 and HL 20220.

² Presented at the Fourth European Complement Workshop, Cambridge, England, December, 1978.

³ Recipient of Fellowship IG58 of the Delegation a la Recherche Scientifique et Technique, France. Present address: Clinique Néphrologique, Hôpital Necker, 161 rue de bevres, 75730 Paris, Cedex 15, France.

⁴ Recipient of Established Investigatorship No. 76-225 of the American Heart Association.

⁵ Cecil H. and Ida M. Green Investigator, in Medical Research, Research Institute of Scripps Clinic.

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