Membranes Under Attack

Science  14 Sep 2007:
Vol. 317, Issue 5844, pp. 1465l
DOI: 10.1126/science.317.5844.1465l

Proteins containing membrane attack complex/perforin (MACPF) domains play an important role in mammalian immune defense by disrupting membranes of invading microorganisms or infected host cells. Two studies and now provide insight into the mechanism of MACPF function. Rosado et al. (p. 1548, published online 23 August 2007) determined the crystal structure of a bacterial MACPF protein at 2.0 angstrom resolution, and Hadders et al. (p. 1552) determined the structure of the MACPF domain of the human complement component C8α at 2.5 angstrom resolution. Surprisingly, both MACPF domains were structurally similar to pore-forming, cholesterol-dependent cytolysins (CDCs) from Gram-positive bacteria. The mechanism of pore formation by CDCs is known, and the structural results suggest that lytic MACPF proteins may use a similar mechanism to disrupt cell membranes.

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