INTERACTION OF TRANSMEMBRANE HELICES BY A KNOBS-INTO-HOLES PACKING CHARACTERISTIC OF SOLUBLE COILED COILS

Membrane-embedded protein domains frequently exist as cc-helical bundl es, as exemplified by photosynthetic reaction centers, bacteriorhodops in, and cytochrome C oxidase. The sidechain packing between their tran smembrane helices was investigated by a nearest-neighbor analysis whic h identified sets of interfacial residues for each analyzed helix-heli x interface. For the left-handed helix-helix pairs, the interfacial re sidues almost exclusively occupy positions a, d, e, or g within a hept ad motif (abcdefg) which is repeated two to three times for each inter acting helical surface. The connectivity between the interfacial resid ues of adjacent helices conforms to the knobs-into-holes type of sidec hain packing known from soluble coiled coils. These results demonstrat e on a quantitative basis that the geometry of sidechain packing is si milar for left-handed helix-helix pairs embedded in membranes and coil ed coils of soluble proteins. The transmembrane helix-helix interfaces studied are somewhat less compact and regular as compared to soluble coiled coils and tolerate all hydrophobic amino acid types to similar degrees, The results are discussed with respect to previous experiment al findings which demonstrate that specific interactions between trans membrane helices are important for membrane protein folding and/or oli gomerization, (C) 1998 Wiley-Liss, Inc.