Studies of transmembrane peptides by pulse dipolar spectroscopy with semi-rigid TOPP spin labels

Tkach, Igor; Diederichsen, Ulf; Bennati, Marina

doi:10.1007/s00249-021-01508-6

Cited by 7 publications

(7 citation statements)

References 109 publications

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“…Dipolar evolution data were acquired using the dead-time free 4-pulse DEER sequence (π/2) obs – (d 1 ) – (π) obs – (d 1 + T) – (π) pump – (d 2 - T) – (π) obs – (d 2 ) – echo( 88 ),( 89 ) with 16-step phase cycling( 90 ). The parameters used for DEER experiments are listed in Table S2.…”

Section: Methodsmentioning

confidence: 99%

Structure and dynamics determine G protein coupling specificity at a class A GPCR

Casiraghi,

Wang,

Brennan

et al. 2024

Preprint

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G protein coupled receptors (GPCRs) activated by their native hormone or neurotransmitter exhibit varying degrees of selectivity for different G protein isoforms. Despite the abundant structures of different GPCR-G protein complexes, little is known about the mechanism of G protein coupling specificity. There are a growing number of examples of pathway-selective or biased synthetic agonists that alter the G protein coupling preference for specific GPCRs. The β2AR is an example of a GPCR with high selectivity for coupling to Gαs, the stimulatory G protein for adenylyl cyclase, and much weaker for the Gi family of G proteins that inhibit adenylyl cyclase. While the Gαs pathway is the major therapeutic target for β2AR agonists, β2ARs have been shown to couple to Gαi isoforms in the heart, and this Gαi signaling may have relevance in the pathogenesis of heart failure. Here we present a new Gαi-biased agonist (LM189) for Gαi activation by the β2AR. We provide structural and biophysical evidence that the Gαi bias of LM189 can be attributed to an alteration in the structure and dynamics of ICL2 and TM6.

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Section: Methodsmentioning

confidence: 99%

Structure and dynamics determine G protein coupling specificity at a class A GPCR

Casiraghi,

Wang,

Brennan

et al. 2024

Preprint

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“…Besides the above-mentioned techniques, pulse dipolar Electron Paramagnetic Resonance spectroscopy (PDS EPR) [36][37][38][39] allows to obtain distance distribution functions between paramagnetic centers, naturally present in the system or artificially introduced via spin-labeling [40][41][42]. EPR is widely used for characterizing the conformation of peptides and proteins.…”

Section: Introductionmentioning

confidence: 99%

“…It should be noted that, depending on the character of the binding (for example, the binding of metal ions through the main peptide chain is usually less selective and less efficient than through side chains [6]) and on the changes in the local peptide structure, the variation of the distance distribution function between labels can be subtle [45][46][47]. In this connection, the so-called rigid or semi-rigid labels, such as the nitroxide-bearing, C α -tetrasubstituted residue TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid, Figure 1) possess a clear advantage in comparison with the typically used spin labels with flexible linkers [42,48]. Indeed, when inserted in the peptide sequence, those rigid labels become reliable probes of any conformational change.…”

Section: Introductionmentioning

confidence: 99%

A Peptide-Based Trap for Metal Ions Studied by Electron Paramagnetic Resonance

et al. 2022

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Peptide-based materials provide a versatile platform for sensing and ion sequestration since peptides are endowed with stimuli-responsive properties. The mechanism of molecular sensing is often based on peptide structural changes (or switching), caused by the binding of the target molecule. One scope of sensing applications is the selection of a specific analyte, which may be achieved by adjusting the structure of the peptide binding site. Therefore, exact knowledge of peptide properties and 3D-structure in the ‘switched’ state is desirable for tuning the detection and for further molecular construction. Hence, here we demonstrate the performance of Electron Paramagnetic Resonance (EPR) spectroscopy in the identification of metal ion binding by the antimicrobial peptide trichogin GA IV. Na(I), Ca(II), and Cu(II) ions were probed as analytes to evaluate the impact of coordination number, ionic radii, and charge. Conclusions drawn by EPR are in line with literature data, where other spectroscopic techniques were exploited to study peptide-ion interactions for trichogin GA IV, and the structural switch from an extended helix to a hairpin structure, wrapped around the metal ion upon binding of divalent cations was proposed.

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“…This tilt angle of transmembrane β-peptides upon reconstitution into a DOPC membrane was determined by X-ray studies with labeled heavy atoms 19 and EPR spectroscopy. 22,23 The concept of a β-peptide 14-helical transmembrane molecular ruler is based on the highly stable helix conformation even when the β-peptide sequence is extended beyond the membrane portion. While in general the conformational stability of a β-peptide 14-helix in water is limited 24 it needs to be stabilized by trans-1-(benzyloxycarbonylamino)-cyclohexyl-2-carboxylic acid (ACHC) 25 or salt bridges.…”

Section: Introductionmentioning

confidence: 99%

Transmembrane β‐peptide helices as molecular rulers at the membrane surface

Martin

Sharma

Enderlein

et al. 2021

Journal of Peptide Science

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β-Peptides are known to form 14-helices with high conformational rigidity, helical persistence length, and well-defined spacing and orientation regularity of amino acid side chains. Therefore, β-peptides are well suited to serve as backbone structures for molecular rulers. On the one hand, they can be functionalized in a site-specific manner with molecular probes or fluorophores, and on the other hand, the β-peptide helices can be recognized and anchored in a biological environment of interest. In this study, the β-peptide helices were anchored in lipid bilayer membranes, and the helices were elongated in the outer membrane environment. The distances of the covalently bound probes to the membrane surface were determined using grapheneinduced energy transfer (GIET) spectroscopy, a method based on the distancedependent quenching of a fluorescent molecule by a nearby single graphene sheet. As a proof of principle, the predicted distances were determined for two fluorophores bound to the membrane-anchored β-peptide molecular ruler.

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Studies of transmembrane peptides by pulse dipolar spectroscopy with semi-rigid TOPP spin labels

Cited by 7 publications

References 109 publications

Structure and dynamics determine G protein coupling specificity at a class A GPCR

Structure and dynamics determine G protein coupling specificity at a class A GPCR

A Peptide-Based Trap for Metal Ions Studied by Electron Paramagnetic Resonance

Transmembrane β‐peptide helices as molecular rulers at the membrane surface

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