Tryptophan Supports Interaction of Transmembrane Helices

• Published in: Journal of molecular biology Vol. 354; no. 4; pp. 894 - 902
• Main Authors: Ridder, Anja, Skupjen, Paulina, Unterreitmeier, Stephanie, Langosch, Dieter
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 09-12-2005
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Amino Acid Substitution; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Cloning, Molecular; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; interaction; Membrane Proteins - chemistry; Membrane Proteins - genetics; Mutagenesis, Site-Directed; Peptide Library; POSSYCCAT; Protein Folding; Protein Structure, Secondary; ToxR; Transcription Factors - chemistry; Transcription Factors - genetics; transmembrane segment; Tryptophan; POSSYCCAT; ToxR; transmembrane segment; CAT; interaction; MU; MalE; CM; TMS; tryptophan; β-gal
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2005.09.084

Interactions of transmembrane helices play an important role in folding and oligomerisation 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.