A

Poly-C9

Figure 1 Model for the mechanism of action of CD59. Two putative binding sites on C5b-8 for C9 are shown. C9 binds loosely in its globular form at site 1 and at this stage may be displaced by other C9 molecules; this may be demonstrated experimentally by holding the temperature at 4°C (A). However, at 37°C C9 normally unfolds and interacts with site 2 on the C5b-8 complex (B), begins to penetrate the cell membrane, and exposes sites for interaction with additional C9 molecules which polymerise to form a transmembrane pore (C). In the presence of CD59, the initial interaction of C9 with C5b-8 occurs, but the binding of CD59 to C8 prevents the C5b-8 catalyzed unfolding and insertion of multiple C9 molecules into the membrane, and thereby blocks cell lysis. (Reproduced with permission of Blackwell Science Ltd, from Men S, Morgan BP, Davies A et al (1990) Human protection (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalyzed insertion of C9 into lipid layers. Immunology 71: 1-9).

Inlhfi presence of CD59

Inlhfi presence of CD59

InsMlon o' a eylolytlenlly iidlve torn of C9 is blocked

InsMlon o' a eylolytlenlly iidlve torn of C9 is blocked

In the absence o! CD59

C9 loosely bwrnj ¡displaceablej

C9 loosely bwrnj ¡displaceablej

C9 unfolding and Itomtlon

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