Inequalities with π<i>N</i>Polarization

Sakmar, I. A.

doi:10.1143/ptp.48.235

Cited by 5 publications

(4 citation statements)

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“…After photon absorption as the initial event of signal transduction, the chromophore undergoes a cis to trans isomerization. Within milliseconds, the resulting structural changes within the chromophore binding pocket, which is situated in the transmembrane region of the receptor apart from the solvent, are propagated to the cytoplasmic surface of the protein (1,3,4). The induced conformational changes on the cytoplasmic side then allow the docking of its cognate G protein transducin and the activation of the visual signal transduction cascade (1).…”

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confidence: 99%

“…The visual pigment rhodopsin belongs to the large class of G protein-coupled receptors (GPCRs), which play a considerable role in signal transduction processes ( − ). It is, as the other members of this family, a transmembrane protein consisting of a bundle of seven membrane-spanning α-helices, which are interconnected by cytoplasmic and extracellular loop regions.…”

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confidence: 99%

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Conformation and Stability of α-Helical Membrane Proteins. 1. Influence of Salts on Conformational Equilibria between Active and Inactive States of Rhodopsin

Vogel

Siebert

2002

Biochemistry

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We studied the influence of salts on the pH-dependent conformational equilibria between the active and the inactive photoproduct states of rhodopsin, Meta II and Meta I, respectively, and between the active and inactive conformations of the apoprotein opsin. In both equilibria, the active species is favored in the presence of medium to high concentration of salt. The ion selectivity for the Meta I/Meta II equilibrium is particularly pronounced for the anions and follows the series trichloroacetate > thiocyanate > iodide > bromide > sulfate > chloride > acetate. The Hill coefficient of this salt-induced transition is close to 2.0. Both ion selectivity and Hill coefficient suggest that the transition is mainly regulated by ion binding to two specific charged binding sites in the protein with smaller contributions being due to the Hofmeister effect. We propose that these putative ion binding sites are identical to those sites that are titrated in the corresponding pH-dependent conformational transition. They presumably function as ionic locks, which keep the receptor in an inactive conformation, and which may be disrupted either by pH-dependent protonation or by salt-dependent ion binding.

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confidence: 99%

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confidence: 99%

Conformation and Stability of α-Helical Membrane Proteins. 1. Influence of Salts on Conformational Equilibria between Active and Inactive States of Rhodopsin

Vogel

Siebert

2002

Biochemistry

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“…Members of these photoactive pigments fall into two distinct subfamilies, the prokaryotic and eukaryotic rhodopsins, respectively [34,35]. Prokaryotic rhodopsins function as light-driven proton pumps (bacteriorhodopsin, archaerhodopsins), light-driven chloride ion pumps (halorhodopsin), and photosensors, mediating photoattractant as well as photophobic responses.…”

Section: Structural Investigations On 7tm Proteinsmentioning

confidence: 99%

“…Unlike the rhodopsins from bacterial sources, the eukaryotic rhodopsins belong to the protein superfamily of GPCRs, thus qualifying them as ideal candidates to derive experimental structure data indicative for that target family, since these proteins also tend to form 2D crystals amenable to electron microscopy and crystallography methods. In contrast to the bacterial rhodopsins that function as ion pumps, eukaryotic rhodopsins are visual pigments that trigger a signal transduction cascade upon light absorption through cytoplasmic G protein-coupling in the outer segment of rod cells of the vertebrate retina, thereby inducing membrane hyperpolarization and nerve excitation [34,35]. Comparative protein sequence analyses reveal amino acid sequence homology of eukaryotic rhodopsins with several members of the GPCR family, supporting not only the functional relation between rhodopsins and GPCRs, but also suggesting that the numerous members of that pharmacologically interesting target family are structurally related to the rhodopsins.…”

Section: Studies On Eukaryotic Rhodopsinsmentioning

confidence: 99%

Towards 3D Structures of G Protein-Coupled Receptors A Multidisciplinary Approach

Müller

2000

CMC

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Current strategies in pharmaceutical research comprise two methodologically different but complementary approaches for lead finding purposes, namely the random screening of compound libraries and the structure-based effort, commonly termed rational drug design. The structure-based approach is aimed to exploit 3D structure data of the molecular components involved in the molecular recognition event that underlies the attempt to therapeutically modulate the biological function of a macromolecular target with proven pathophysiological relevance for a disease state. In this context, G protein-coupled receptors (GPCRs) constitute the most prominent family of validated drug targets within biomedical research, since approximately 60 % of approved drugs elicit their therapeutic effects by selectively addressing members of that target family. From a 3D structure point of view, these transmembrane signal transduction systems represent the most challenging task for structure determination, which is due to the heterogeneous and fine-balanced environment conditions that are necessary for structural and functional integrity of the receptor protein. This contribution will address the different concepts to derive structurally relevant information on the transmemebrane seven-helix protein (7TM) domain of GPCRs with special emphasis laid on the multidisciplinarity of the applied methodologies. The current status of electron-cryo-microscopy on 2D crystals and even high-resolution x-ray crystallography on 7TM proteins will be introduced highlighting the transferability of the emerging structural principles onto the GPCR superfamily. Special techniques from bioinformatics and homology-related molecular modeling in combination with tailor-made protein simulation methodologies complement the experimentally derived data, in that they facilitate the 3D structure generation and structure validation process. This contribution summarises the most recent results of GPCR structure studies with the aim to underline the impact of structure data not only for the purpose of rationalising structure-activity data on low-molecular weight antagonists within the context of a protein binding pocket, but also for a better understanding of e.g. mutagenesis experiments, thus qualifying GPCR structure models as valid communication platforms establishing a functional link between molecular biology, biophysics, bioinformatics and organic chemistry in a highly efficient manner.

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Tests of bounds obtained from experimental π-N polarization and differential cross section

Liu

Sakmar

1973

Annals of Physics

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Inequalities with πNPolarization

Cited by 5 publications

References 1 publication

Conformation and Stability of α-Helical Membrane Proteins. 1. Influence of Salts on Conformational Equilibria between Active and Inactive States of Rhodopsin

Conformation and Stability of α-Helical Membrane Proteins. 1. Influence of Salts on Conformational Equilibria between Active and Inactive States of Rhodopsin

Towards 3D Structures of G Protein-Coupled Receptors A Multidisciplinary Approach

Tests of bounds obtained from experimental π-N polarization and differential cross section

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