Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis

Details

Serval ID
serval:BIB_0202B345A7A8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Structural/functional similarity between proteins involved in complement- and cytotoxic T-lymphocyte-mediated cytolysis
Journal
Nature
Author(s)
Tschopp  J., Masson  D., Stanley  K. K.
ISSN
0028-0836 (Print)
Publication state
Published
Issued date
09/1986
Volume
322
Number
6082
Pages
831-4
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 28-Sep 3
Abstract
Cytolysis mediated by complement or cytolytic lymphocytes results in the formation of morphology similar lesions in the target membrane. These lesions, formed by the polymerization of C9 or perforin respectively, contribute the major killing action by causing osmotic lysis of the target cell. Following the suggestion of Mayer that the mechanisms of humoral and cell-mediated cytotoxicity might be related, studies into the morphology of the membrane lesions formed, and the proteins responsible for causing the lesions, have shown several similarities. While the lesion caused by natural and T-killer cells is a little larger than that caused by complement, its overall shape is similar and in both cases the cylindrical pore is formed by polymerization of a monomeric subunit, C9 (relative molecular mass, Mr = 71,000) for complement, and perforin (Mr = 66,000) for cell-mediated cytotoxicity. C9 has an absolute requirement for a receptor in the target membrane formed by the earlier membrane attack complex components, C5b, C6, C7 and C8 (ref. 8). For perforin, polymerization in a target membrane requires no receptor, specificity being derived from the specific recognition between killer and target cell. Both proteins can be made to polymerize in vitro by the addition of divalent cations (Zn2+ for C9 (ref. 16) and Ca2+ for perforin) and the resultant complexes closely resemble their physiological counterparts. Antibodies raised against lymphocyte-killed targets have also been shown to cross-react with complement proteins, but the antigenically related proteins were not determined in these studies. We show here using purified proteins that perforin, C9 and complexes involving C7 and C8 share a common antigenic determinant which is probably involved in polymerization.
Keywords
Amino Acid Sequence Biopolymers Cell Membrane/ultrastructure Complement C9/antagonists & inhibitors/genetics/*physiology Complement Membrane Attack Complex Complement System Proteins/genetics/*physiology *Cytotoxicity, Immunologic Epitopes *Membrane Glycoproteins Membrane Proteins/antagonists & inhibitors/genetics/*physiology Peptide Fragments/pharmacology Pore Forming Cytotoxic Proteins Receptors, LDL/genetics Sequence Homology, Nucleic Acid Suramin/pharmacology T-Lymphocytes, Cytotoxic/*immunology
Pubmed
Web of science
Create date
24/01/2008 15:18
Last modification date
20/08/2019 12:24
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