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The alternative pathway of complement

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Conclusions

The molecular mechanisms of the alternative pathway are now reasonably well understood. Intramolecular functional sites are currently being delineated that govern the crucial interactions between C3 and the other proteins of the pathway. The knowledge of the primary structure of C3 is affording the synthesis of small peptides that may aid the identification of functional regions. Should the three-dimensional structure of C3 or C3b become available, information on functional regions may readily be incorporated into the molecular model. Uncertain remains the mechanism of recognition utilized by the alternative pathway to distinguish between activators and nonactivators. This ability resides in C3b and Factor H which jointly constitute the recognition unit. But how this simple bimolecular recognition unit senses cell surface structures is unknown. The relatively recent awareness of cell surface regulators of complement has led to the description of a molecular defect in an acquired hemolytic anemia. The biologic role of these membrane proteins and their occurrence on cells other than erythrocytes will have to be determined. Also, both CRI and DAF share functional properties with Factor H and C4 binding protein and it is probable that the functional homologies have structural correlates. Thus these four proteins together with properdin constitute a group of apparently interrelated binding proteins that function as regulators of the C3/C5 convertases. Structural information on the protein or cDNA level is needed to assess the degree of interrelatedness between these plasma and membrane proteins.

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  1. Michael K. Pangburn

    Present address: Department of Biochemistry, The University of Texas Health Center at Tyler, P. O. Box 2003, 75710, Tyler, Texas, USA

Authors and Affiliations

  1. Department of Immunology (IM 10), Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, 92037, La Jolla, California, USA

    Michael K. Pangburn & Hans J. Müller-Eberhard

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  1. Michael K. Pangburn
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  2. Hans J. Müller-Eberhard
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This is Publication Number 3573-IMM from the Research Institute of Scripps Clinic

This work was supported by United States Public Health Service Grants AI 17354, CA 27489 and HL 16411

Dr. Müller-Eberhard is the Cecil H. and Ida M. Green Investigator in Medical Research, Research Institute of Scripps Clinic

This work was done during the tenure of an Established Investigatorship (No. 81-225) from the American Heart Association and with funds contributed in part by the A. H. A. California Affiliate

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Pangburn, M.K., Müller-Eberhard, H.J. The alternative pathway of complement. Springer Semin Immunopathol 7, 163–192 (1984). https://doi.org/10.1007/BF01893019

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