Tryptophan Residues Flanking the Second Transmembrane Helix (TM2) Set the Signaling State of the Tar Chemoreceptor†

Biochemistry ◽  
2005 ◽  
Vol 44 (4) ◽  
pp. 1268-1277 ◽  
Author(s):  
Roger R. Draheim ◽  
Arjan F. Bormans ◽  
Run-zhi Lai ◽  
Michael D. Manson
Keyword(s):  
Transmembrane Helix ◽  
Tryptophan Residues

scholarly journals Kinetics of pHLIP peptide insertion into and exit from a membrane

2020 ◽  
Vol 117 (22) ◽  
pp. 12095-12100
Author(s):  
Gregory Slaybaugh ◽  
Dhammika Weerakkody ◽  
Donald M. Engelman ◽  
Oleg A. Andreev ◽  
Yana K. Reshetnyak
Keyword(s):  
Lipid Bilayer ◽  
Transmembrane Helix ◽  
Peptide Folding ◽  
Tryptophan Residues ◽  
N Terminus ◽  
Mechanistic Understanding ◽  
Peptide Insertion ◽  
Kinetics Of ◽  
Different Parts

To advance mechanistic understanding of membrane-associated peptide folding and insertion, we have studied the kinetics of three single tryptophan pHLIP (pH-Low Insertion Peptide) variants, where tryptophan residues are located near the N terminus, near the middle, and near the inserting C-terminal end of the pHLIP transmembrane helix. Single-tryptophan pHLIP variants allowed us to probe different parts of the peptide in the pathways of peptide insertion into the lipid bilayer (triggered by a pH drop) and peptide exit from the bilayer (triggered by a rise in pH). By using pH jumps of different magnitudes, we slowed down the processes and established the intermediates that helped us to understand the principles of insertion and exit. The obtained results should also aid the applications in medicine that are now entering the clinic.

scholarly journals Influence of interfacial tryptophan residues on an arginine-flanked transmembrane helix

2020 ◽  
Vol 1862 (2) ◽  
pp. 183134
Author(s):  
Sara J. Sustich ◽  
Fahmida Afrose ◽  
Denise V. Greathouse ◽  
Roger E. Koeppe
Keyword(s):  
Transmembrane Helix ◽  
Tryptophan Residues

scholarly journals Interfacial Tryptophan Residues Govern Transmembrane Helix Dynamics

2017 ◽  
Vol 112 (3) ◽  
pp. 528a
Author(s):  
Matthew J. McKay ◽  
Ashley N. Martfeld ◽  
Anna A. De Angelis ◽  
Stanley J. Opella ◽  
Denise V. Greathouse ◽  
...  
Keyword(s):  
Transmembrane Helix ◽  
Tryptophan Residues

scholarly journals Control of Transmembrane Helix Dynamics by Interfacial Tryptophan Residues

2018 ◽  
Vol 114 (11) ◽  
pp. 2617-2629 ◽  
Author(s):  
Matthew J. McKay ◽  
Ashley N. Martfeld ◽  
Anna A. De Angelis ◽  
Stanley J. Opella ◽  
Denise V. Greathouse ◽  
...  
Keyword(s):  
Transmembrane Helix ◽  
Tryptophan Residues

Coaction of Electrostatic and Hydrophobic Interactions: Dynamic Constraints on Disordered TrkA Juxtamembrane Domain

2019 ◽  
Author(s):  
Zichen Wang ◽  
Huaxun Fan ◽  
Xiao Hu ◽  
John Khamo ◽  
Jiajie Diao ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Function ◽  
Hydrophobic Interactions ◽  
Transmembrane Helix ◽  
Point Mutations ◽  
Salt Bridge ◽  
Receptor Activation ◽  
Membrane Dynamics ◽  
Juxtamembrane Domain ◽  
Joint Work

<p>The receptor tyrosine kinase family transmits signals into cell via a single transmembrane helix and a flexible juxtamembrane domain (JMD). Membrane dynamics makes it challenging to study the structural mechanism of receptor activation experimentally. In this study, we employ all-atom molecular dynamics with Highly Mobile Membrane-Mimetic to capture membrane interactions with the JMD of tropomyosin receptor kinase A (TrkA). We find that PIP<sub>2 </sub>lipids engage in lasting binding to multiple basic residues and compete with salt bridge within the peptide. We discover three residues insertion into the membrane, and perturb it through computationally designed point mutations. Single-molecule experiments indicate the contribution from hydrophobic insertion is comparable to electrostatic binding, and in-cell experiments show that enhanced TrkA-JMD insertion promotes receptor ubiquitination. Our joint work points to a scenario where basic and hydrophobic residues on disordered domains interact with lipid headgroups and tails, respectively, to restrain flexibility and potentially modulate protein function.</p>

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