Tryptophan supports interaction of transmembrane helices.
Interactions of transmembrane helices play an important role in folding and oligomerization of integral membrane proteins. The interfacial residues of these helices frequently correspond to heptad repeat motifs. In order to uncover novel mechanisms underlying these interactions, we randomised a heptad repeat pattern with a complete set of amino acids. Those sequences that were capable of high-affinity self-interaction upon integration into bacterial inner membranes were selected by means of the POSSYCCAT system. A comparison between selected and non-selected sequences reveals that high-affinity sequences were strongly enriched in tryptophan residues that accumulated at specific positions of the heptad motif. Mutation of Trp in selected clones significantly reduced self-interaction of the transmembrane segments without affecting their efficiency of membrane integration. Conversely, grafting Trp onto artificial transmembrane segments strongly enhanced their interaction. We conclude that tryptophan supports interaction of transmembrane segments.
Ridder
Anja
A
Technische Universität München, Lehrstuhl für Chemie der Biopolymere Weihenstephaner Berg 3, D-85354 Freising-Weihenstephan, Germany.
Skupjen
Paulina
P
Unterreitmeier
Stephanie
S
Langosch
Dieter
D
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D019151:Peptide Library; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics; D014364:Tryptophan
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D019151:Peptide Library; D014157:Transcription Factors; C066719:toxR protein, bacteria; D014364:Tryptophan