Figure 10-8: The “death raft” model for holin function. A. Holin rafts. It is proposed that holins accumulate in rafts in the membrane, shown here in a schematic top-down view, and that intimate intermolecular and intramolecular helix-packing between the TMDs of the holins largely excludes lipids. Each circle represents a single holin molecule. Spontaneous formation of an aqueous channel by thermal fluctuation is depicted. The localized depolarization causes a conformational change in the holins leading to asymmetric disruption of the helix packing, exposure of a relatively hydrophilic surface, and dispersion of the subunits into the holin lesion. B. “Hole” size. Based on the raft model above, a rationale for the formation of different-sized lesions by holins, depicted in a cross-sectional schematic of the membrane. Large lesions would be formed by the triggering of the large rafts of holin #1, whereas smaller lesions are formed in #2, which could represent a mutant of holin #1 or a heterologous holin that normally functions with a sec-exported endolysin and thus is not required to form a large lesion to allow endolysin release. Adapted from Wang et al. (110), with permission.