Conformational changes upon binding of a receptor loop to lipid structures: possible role in signal transduction

Pertinhez, Thelma A.; Nakaie, Clóvis R.; Carvalho, R. S. H.; Paiva, Antonio C. M.; Tabak, Marcel; Toma, Flavio; Schreier, Shirley

doi:10.1016/0014-5793(95)01222-z

Cited by 24 publications

(11 citation statements)

References 34 publications

(5 reference statements)

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“…Thus, while the peptide bound to negatively charged SDS, positively charged CTAB, zwitterionic LPC and HPS, and neutral Brij-35 micelles, it interacted with DMPG vesicles only at low pH, both in the gel and in the liquid crystalline phase. CD and steady-state fluorescence measurements corroborated these findings (Pertinhez-Sini et al 1994; Pertinhez et al 1995, 1997). Partition coefficients were calculated from the estimation of free and membrane-bound populations in the peptide EPR spectra.…”

Section: Biologically Active Peptides: Ligands and Fragments Of G Promentioning

confidence: 62%

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

et al. 2012

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We review work on the paramagnetic amino acid 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, TOAC, and its applications in studies of peptides and peptide synthesis. TOAC was the first spin label probe incorporated in peptides by means of a peptide bond. In view of the rigid character of this cyclic molecule and its attachment to the peptide backbone via a peptide bond, TOAC incorporation has been very useful to analyze backbone dynamics and peptide secondary structure. Many of these studies were performed making use of EPR spectroscopy, but other physical techniques, such as X-ray crystallography, CD, fluorescence, NMR, and FT-IR, have been employed. The use of double-labeled synthetic peptides has allowed the investigation of their secondary structure. A large number of studies have focused on the interaction of peptides, both synthetic and biologically active, with membranes. In the latter case, work has been reported on ligands and fragments of GPCR, host defense peptides, phospholamban, and β-amyloid. EPR studies of macroscopically aligned samples have provided information on the orientation of peptides in membranes. More recent studies have focused on peptide–protein and peptide–nucleic acid interactions. Moreover, TOAC has been shown to be a valuable probe for paramagnetic relaxation enhancement NMR studies of the interaction of labeled peptides with proteins. The growth of the number of TOAC-related publications suggests that this unnatural amino acid will find increasing applications in the future.

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Section: Biologically Active Peptides: Ligands and Fragments Of G Promentioning

confidence: 62%

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

et al. 2012

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“…While the role of phospholipids in bacterial signal transduction has not been directly investigated, a number of studies carried out with eukaryotic signal transduction systems demonstrate an important role for proteinlipid interactions for their function. The phospholipid environment (polar headgroup and acyl chain composition) has been shown to affect the structural and functional properties of membrane-bound receptors such as rhodopsin (11), the insulin receptor (21), and a receptor loop of the protein expressed by the mas oncogene (30). A special role of PE, because of its ability to promote formation of nonlamellar phases, was pointed out in studies of the conformational transition of metarhodopsin as a trigger for an intracellular enzyme cascade (11).…”

Section: Discussionmentioning

confidence: 99%

The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine

Mileykovskaya¹,

Dowhan²

1997

J Bacteriol

137

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The CpxA-CpxR two-component signal transduction pathway of Escherichia coli was studied in a mutant (pss-93) lacking phosphatidylethanolamine (PE). Several properties of this mutant are comparable to phenotypes of cpxA point mutants, indicating that this two-component pathway is activated in PE-deficient cells. In contrast to point mutants, cpx operon null mutants have a wild-type phenotype. By use of this information, a cpx operon null allele was introduced into a pss-93 mutant. Certain altered properties of PE-deficient mutants, which were consistent with activation of the Cpx pathway, returned to the wild-type phenotype, namely, active accumulation of proline and thiomethyl-␤-D-galactopyranoside was partially restored to wild-type levels, increased resistance to amikacin returned to wild-type sensitivity, and high levels of degP expression returned to repressed wild-type levels. Elevated levels of acetyl phosphate and nlpE gene product can result in activation of the Cpx pathway. However, inactivation of the nlpE gene or mutations eliminating the ability to make acetyl phosphate did not alter the high level of degP expression in pss-93 mutants. We propose that the lack of PE results in an alteration in cell envelope structure or physical properties, leading to direct activation of the Cpx pathway.

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“…43 The probe's C a -tetrasubstituted cyclic structure favors acquisition of helical structure, as well as turn formation 44,45 and renders the EPR spectra of labeled (macro)molecules highly sensitive to the backbone conformational properties. Owing to these unique characteristics, a large number of studies focusing on peptides, including our own 28,[46][47][48][49][50][51][52][53][54][55][56][57][58] and from a variety of groups [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74] appeared in the literature in recent years. In addition to its applications in structural studies of peptides, TOAC has also been used advantageously in solid phase peptide synthesis to monitor peptide chain assembly throughout the polymer backbone.…”

Section: Introductionmentioning

confidence: 99%

Conformational properties of angiotensin II and its active and inactive TOAC‐labeled analogs in the presence of micelles. Electron paramagnetic resonance, fluorescence, and circular dichroism studies

et al. 2009

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The interaction between angiotensin II (AII, DRVYIHPF) and its analogs carrying 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) and detergents--negatively charged sodium dodecyl sulfate (SDS) and zwitterionic N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS)--was examined by means of EPR, CD, and fluorescence. EPR spectra of partially active TOAC1-AII and inactive TOAC3-AII in aqueous solution indicated fast tumbling, the freedom of motion being greater at the N-terminus. Line broadening occurred upon interaction with micelles. Below SDS critical micelle concentration, broader lines indicated complex formation with tighter molecular packing than in micelles. Small changes in hyperfine splittings evinced TOAC location at the micelle-water interface. The interaction with anionic micelles was more effective than with zwitterionic micelles. Peptide-micelle interaction caused fluorescence increase. The TOAC-promoted intramolecular fluorescence quenching was more pronounced for TOAC3-AII because of the proximity between the nitroxide and Tyr4. CD spectra showed that although both AII and TOAC1-AII presented flexible conformations in water, TOAC3-AII displayed conformational restriction because of the TOAC-imposed bend (Schreier et al., Biopolymers 2004, 74, 389). In HPS, conformational changes were observed for the labeled peptides at neutral and basic pH. In SDS, all peptides underwent pH-dependent conformational changes. Although the spectra suggested similar folds for AII and TOAC1-AII, different conformations were acquired by TOAC3-AII. The membrane environment has been hypothesized to shift conformational equilibria so as to stabilize the receptor-bound conformation of ligands. The fact that TOAC3-AII is unable to acquire conformations similar to those of native AII and partially active TOAC1-AII is probably the explanation for its lack of biological activity.

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Conformational changes upon binding of a receptor loop to lipid structures: possible role in signal transduction

Cited by 24 publications

References 34 publications

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

The Cpx two-component signal transduction pathway is activated in Escherichia coli mutant strains lacking phosphatidylethanolamine

Conformational properties of angiotensin II and its active and inactive TOAC‐labeled analogs in the presence of micelles. Electron paramagnetic resonance, fluorescence, and circular dichroism studies

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