Antiparallel channel models

The most likely way for pardaxin molecules to insert across the membrane in an antiparallel manner is for them to form antiparallel aggregates on the membrane surface that then insert across the membrane. We developed a "raft"model (data not shown) that is similar to the channel model except that adjacent dimers are related to each other by a linear translation instead of a 60 rotation about a channel axis. All of the large hydrophobic side chains of the C-helices are on one side of the "raft" and all hydrophilic side chains are on the other side. We postulate that these "rafts" displace the lipid molecules on one side of the bilayer. When two or more "rafts" meet they can insert across the membrane to form a channel in a way that never exposes the hydrophilic side chains to the lipid alkyl chains. The conformational change from the "raft" to the channel structure primarily involves a pivoting motion about the "ridge" of side chains formed by Thr-17, Ala-21, Ala-25, and Ser-29. These small side chains present few steric barriers for the postulated conformational change. 

We have developed a series of models in which 8-12 monomers were packed in an antiparallel manner to form the channel. The kinetics of pore formation in liposomes (9) and the dependence of planar bilayer conductance on toxin... 

Parallel and antiparallel self-assembly can be differentiated by voltage dependence Parallel self-assembly of asymmetric monomers gives voltage-sensitive, antiparallel self-assembly voltage-insensitive synthetic ion channels and pores [9]. Other indirect evidence from function such as inner diameters from Hill analysis of single-channel conductance (Section 11.3.3) or other size exclusion experiments is often used to support indications for supramolecular active structures molecular modeling can be of help as well [3, 4, 10]. 

Figure 3 The packing of a pair of bent helical molecules of [Leu ]zervamicin is shown schematically (left) and in the form of an atomic model derived from an X-ray crystal structure determination (right). The latter corresponds to one of the crystal forms represented by one of the three superimposed envelopes of [Leu ]zervamicin (solid, dotted, and dashed lines) in the schema. The polar faces of the pair of helices associate in an antiparallel fashion, and thereby form a discontinuous water channel. The channel is closed in the middle by interpeptide hydrogen bonds involving backbone carbonyls 0(6) and 0(7) and side chain moieties O (Hyp ) and N (Gin"). The heavier dashed lines in the center of the atomic model show the interpeptide hydrogen bonds. In a more recent study, about 20% of the water channels were found to be open as a consequence of a rotation of the side chain of Gin" and the subsequent formation of intrapeptide hydrogen bonds...

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