Differential repositioning of the second transmembrane helices from E. coli Tar and EnvZ upon moving the flanking aromatic residues

Aromatic tuning, i.e. repositioning aromatic residues found at the cytoplasmic end of transmembrane (TM) domains within bacterial receptors, has been previously shown to modulate signal output from the aspartate chemoreceptor (Tar) and the major osmosensor EnvZ of Escherichia coli. In the case of Ta...

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Published in:	Biochimica et biophysica acta Vol. 1848; no. 2; pp. 615 - 621
Main Authors:	Botelho, Salomé C., Enquist, Karl, von Heijne, Gunnar, Draheim, Roger R.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-02-2015
Subjects:	Amino Acid Motifs Aromatic tuning Bacterial Outer Membrane Proteins - chemistry Cell Membrane - chemistry Cell Membrane - metabolism Cytoplasm - chemistry Cytoplasm - metabolism Escherichia coli - chemistry Escherichia coli - metabolism Escherichia coli Proteins - chemistry Glycosylation mapping Hydrophobic-polar membrane interface Interfacial anchoring Leucine - chemistry Molecular Dynamics Simulation Molecular Sequence Data Multienzyme Complexes - chemistry Phenylalanine - chemistry Protein Structure, Secondary Receptors, Cell Surface - chemistry Sequence Alignment Signal Transduction Structure-Activity Relationship Transmembrane helices Tryptophan - chemistry AS2 Glycosylation mapping Aromatic tuning MGD CG-MD Hydrophobic-polar membrane interface SHK WALP or YALP TM2 TM RM Interfacial anchoring Transmembrane helices AS1
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Summary:	Aromatic tuning, i.e. repositioning aromatic residues found at the cytoplasmic end of transmembrane (TM) domains within bacterial receptors, has been previously shown to modulate signal output from the aspartate chemoreceptor (Tar) and the major osmosensor EnvZ of Escherichia coli. In the case of Tar, changes in signal output consistent with the vertical position of the native Trp-Tyr aromatic tandem within TM2 were observed. In contrast, within EnvZ, where a Trp-Leu-Phe aromatic triplet was repositioned, the surface that the triplet resided upon was the major determinant governing signal output. However, these studies failed to determine whether moving the aromatic residues was sufficient to physically reposition the TM helix within a membrane. Recent coarse-grained molecular dynamics (CG-MD) simulations predicted displacement of Tar TM2 upon moving the aromatic residues at the cytoplasmic end of the helix. Here, we demonstrate that repositioning the Trp-Tyr tandem within Tar TM2 displaces the C-terminal boundary of the helix relative to the membrane. In a similar analysis of EnvZ, an abrupt initial displacement of TM2 was observed but no subsequent movement was seen, suggesting that the vertical position of TM2 is not governed by the location of the Trp-Leu-Phe triplet. Our results also provide another set of experimental data, i.e. the resistance of EnvZ TM2 to being displaced upon aromatic tuning, which could be useful for subsequent refinement of the initial CG-MD simulations. Finally, we discuss the limitations of these methodologies, how moving flanking aromatic residues might impact steady-state signal output and the potential to employ aromatic tuning in other bacterial membrane-spanning receptors. [Display omitted] •Aromatic tuning with a Trp-Tyr tandem displaces Tar TM2 in a membrane.•Displacement of Tar TM2 consistent with previous coarse grained molecular dynamics (CG-MD) simulations.•Repositioning the Trp-Leu-Phe triplet does not incrementally displace EnvZ TM2.•Propensity for TM2 displacement agrees with previous patterns of tuned signal output.
ISSN:	0005-2736 0006-3002 1879-2642 1879-2642
DOI:	10.1016/j.bbamem.2014.11.017