Interaction of transmembrane helices by a knobs-into-holes packing characteristic of soluble coiled coils.
Membrane-embedded protein domains frequently exist as alpha-helical bundles, as exemplified by photosynthetic reaction centers, bacteriorhodopsin, and cytochrome C oxidase. The sidechain packing between their transmembrane helices was investigated by a nearest-neighbor analysis which identified sets of interfacial residues for each analyzed helix-helix interface. For the left-handed helix-helix pairs, the interfacial residues almost exclusively occupy positions a, d, e, or g within a heptad motif (abcdefg) which is repeated two to three times for each interacting helical surface. The connectivity between the interfacial residues of adjacent helices conforms to the knobs-into-holes type of sidechain packing known from soluble coiled coils. These results demonstrate on a quantitative basis that the geometry of sidechain packing is similar for left-handed helix-helix pairs embedded in membranes and coiled 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 experimental findings which demonstrate that specific interactions between transmembrane helices are important for membrane protein folding and/or oligomerization.
Langosch
D
D
Department of Neurobiology, Universität Heidelberg, Germany. langosch@sun0.urz.uni-heidelberg.de
Heringa
J
J
D000465:Algorithms; D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000737:chemistry; D003576:Electron Transport Complex IV / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D045322:Photosynthetic Reaction Center Complex Proteins / Q000737:chemistry; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012995:Solubility
D008565:Membrane Proteins; D045322:Photosynthetic Reaction Center Complex Proteins; D001436:Bacteriorhodopsins; D003576:Electron Transport Complex IV