title: A heptad motif of leucine residues found in membrane proteins can drive self-assembly of artificial transmembrane segments.
abstract: Specific interactions between alpha-helical transmembrane segments are important for folding and/or oligomerization of membrane proteins. Previously, we have shown that most transmembrane helix-helix interfaces of a set of crystallized membrane proteins are structurally equivalent to soluble leucine zipper interaction domains. To establish a simplified model of these membrane-spanning leucine zippers, we studied the homophilic interactions of artificial transmembrane segments using different experimental approaches. Importantly, an oligoleucine, but not an oligoalanine, se- quence efficiently self-assembled in membranes as well as in detergent solution. Self-assembly was maintained when a leucine zipper type of heptad motif consisting of leucine residues was grafted onto an alanine host sequence. Analysis of point mutants or of a random sequence confirmed that the heptad motif of leucines mediates self-recognition of our artificial transmembrane segments. Further, a data base search identified degenerate versions of this leucine motif within transmembrane segments of a variety of functionally different proteins. For several of these natural transmembrane segments, self-interaction was experimentally verified. These results support various lines of previously reported evidence where these transmembrane segments were implicated in the oligomeric assembly of the corresponding proteins.
authors: Universität Heidelberg, Neurobiology Department, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
authors: R
authors: R
authors: Gurezka
authors: R
authors: R
authors: Laage
authors: B
authors: B
authors: Brosig
authors: D
authors: D
authors: Langosch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D002645:Chickens; D002850:Chromatography, Gel; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016208:Databases, Factual; D006801:Humans; D007930:Leucine / Q000378:metabolism*; D016350:Leucine Zippers / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014981:Xenopus
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D014157:Transcription Factors; C066719:toxR protein, bacteria; D007930:Leucine