Modeling of transmembrane seven helix bundles

Cronet, Philippe; Sander, Chris; Vriend, Gert

doi:10.1093/protein/6.1.59

Cited by 102 publications

(59 citation statements)

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“…The upfield chemical shifts of the CaH, the decrease of all 'JNFr-caH coupling constants and the calculated NH,-NH,,,, CaH,-NH,,, distances demonstrate the existence of a-helical structures for residues (2-6) and (10)(11)(12)(13)(14), with the N-terminal Ala being preferentially in an extended conformation as shown by the dNN Alal -Met2 distance. Low temperature coefficients for adjacent residues indicate that these helical conformations exist simultaneously in a single structure.…”

Section: Conformation In Perfluoro-tert-butanoycdod (9 : 1)mentioning

confidence: 80%

“…So, whatever the internal reference taken from the peptidic backbone, i.e. inter-or intra-residue distances, the resulting dNN distances between amide protons of adjacent residues in the (2-6) and (10)(11)(12)(13)(14) regions are close to the ideal 0.27-nm value, whereas d,, distances between CaH,-NH,,, range over 0.31 -0. 35 20.01 nm (ideal value for a-helical structure 0.36 nm).…”

Section: Residuementioning

confidence: 93%

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Three‐Dimensional Structure of the Highly Conserved Seventh Transmembrane Domain of G‐Protein‐Coupled Receptors

Berlose

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Brunissen

et al. 1994

European Journal of Biochemistry

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The S/T-XI-X,-N-P-X,-X,-Y highly conserved sequence of the seventh transmembrane (TM VII) segment of G-protein-coupled receptors is not present in the photon receptor bacteriorhodopsin TM VII domain. Despite this noticeable discrepancy in sequence, the X-ray structure of bacteriorhodopsin is generally used as the key structure for modelling all G-protein-coupled receptors. Thus, a kinked truns-Pro helix is usually accepted for the TM VII three-dimensional structure of G-proteincoupled receptors, although Asn-Pro dipeptide mainly induces a type UIII /3-turn conformation in both model peptides and proteins. NMR studies in various solvents and molecular calculations were undertaken in order to gain insight into the conformational behaviour of a 15-residue peptide from the tachykinin NK-1 TM VII domain incorporating this common sequence. The low solubility of this membrane-embedded peptide precludes methanol or micellar systems mimicking membrane environment; thus only dimethylsulfoxide (Me,SO) or chlorofonn/Me,SO mixture could be used. We also found that perfluoro-tert-butanol, which has not been previously used for NMR studies, constitutes an excellent alternative solvent for the analysis of hydrophobic peptides. The postulated kinked truns-Pro helix was only present as a minor conformer in Me,SO and an equilibrium between helical and extended structures existed. From NOE data a type I/III ,&structure, centered around Pro9-Ile10, probably stabilized by an Asx turn, may be postulated. Addition of chloroform in Me,SO increased the percentage of folded structures but no preferential conformation could be proposed. In perfluoro-tert-butanoI/CD,OD (9 : 1) the N-and C-terminal regions presented an a-helical structure, and these two domains were linked by a hinge around Asn-Pro with a y-turn for the preceding residue Tyr7 and either a type I/III p-turn around Pro9-IlelO or cxR orientations for these residues, which are both stabilized by an Asx turn. As determined by energy calculations, these structures were equally as stable as the kinked truns-Pro helix and could constitute key structures for analysing the conformational changes and/or the dynamics of TM VII segment induced by the ligand when interacting with the receptor.The apparent similarity in the hydropathicity profiles of G-protein-coupled receptors [ 1 -41 with that of bacteriorhodopsin [5] has led to the use of this integral membrane protein as a starting point for predicting their three-dimensional structures [6-121, even though bacteriorhodopsin is not coupled to G-proteins. The currently accepted proposal for the topography of G-protein-coupled receptors includes seven transmembrane-spanning domains (TM I-VII) joined together by extracellular and cytoplasmic loops, with the Nterminal side in the extracellular cleft and the C-terminal residues in the cytoplasm. This model, which was first deduced Correspondence to S .

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Section: Conformation In Perfluoro-tert-butanoycdod (9 : 1)mentioning

confidence: 80%

Section: Residuementioning

confidence: 93%

Three‐Dimensional Structure of the Highly Conserved Seventh Transmembrane Domain of G‐Protein‐Coupled Receptors

Berlose

Convert

Brunissen

et al. 1994

European Journal of Biochemistry

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“…(19), the mammal Bos taurus (20), and the bacterium Paracoccus denitrificans (21). Identification of covarying pairs of residues in the sequences of homologous proteins, also known as evolutionary couplings, can identify pairs of residues that are likely to interact physically (22)(23)(24)(25). A model was proposed for the a subunit from the mammalian ATP synthase using data from evolutionary covariance in conjunction with the cryo-EM density map (20).…”

Section: Significancementioning

confidence: 99%

Models for the a subunits of the Thermus thermophilus V/A-ATPase and Saccharomyces cerevisiae V-ATPase enzymes by cryo-EM and evolutionary covariance

Schep

Zhao

Rubinstein

2016

Proc. Natl. Acad. Sci. U.S.A.

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Rotary ATPases couple ATP synthesis or hydrolysis to proton translocation across a membrane. However, understanding proton translocation has been hampered by a lack of structural information for the membrane-embedded a subunit. The V/A-ATPase from the eubacterium Thermus thermophilus is similar in structure to the eukaryotic V-ATPase but has a simpler subunit composition and functions in vivo to synthesize ATP rather than pump protons. We determined the T. thermophilus V/A-ATPase structure by cryo-EM at 6.4 Å resolution. Evolutionary covariance analysis allowed tracing of the a subunit sequence within the map, providing a complete model of the rotary ATPase. Comparing the membraneembedded regions of the T. thermophilus V/A-ATPase and eukaryotic V-ATPase from Saccharomyces cerevisiae allowed identification of the α-helices that belong to the a subunit and revealed the existence of previously unknown subunits in the eukaryotic enzyme. Subsequent evolutionary covariance analysis enabled construction of a model of the a subunit in the S. cerevisae V-ATPase that explains numerous biochemical studies of that enzyme. Comparing the two a subunit structures determined here with a structure of the distantly related a subunit from the bovine F-type ATP synthase revealed a conserved pattern of residues, suggesting a common mechanism for proton transport in all rotary ATPases.cryo-EM | evolutionary covariance | V-ATPase | V/A-ATPase | structure V acuolar H + -ATPases (V-ATPases) are large membrane protein complexes responsible for the acidification of intracellular compartments in eukaryotes. These complexes are essential for processes including receptor-mediated endocytosis, coupled transport, and lysosomal degradation (1). V-ATPases localize to the plasma membrane of some specialized cells where they participate in bone resorption by osteoclasts (2) and urine acidification by the α-intercalated cells of the kidney (3). Malfunction or misregulation of these enzymes results in numerous disorders, including osteopetrosis (4) and renal tubular acidosis (5, 6). Expression of V-ATPases on the surfaces of some tumor cells results in increased tumor invasion and metastasis (7). The V/A-ATPase from the thermophilic eubacterium Thermus thermophilus is homologous to the eukaryotic V-ATPase and has a similar overall structure, but is smaller and simpler and functions in vivo as an ATP synthase. V-and V/A-ATPases have similar subunit folds and arrangements of subunits (8-11). The simplified architecture and superior stability of the T. thermophilus V/A-ATPase make it an ideal model to study the structure and function of V-ATPases. Both enzymes are composed of a soluble V 1 catalytic region and a membrane-embedded V O region. The V/A-ATPase subunits I, L, and C in T. thermophilus are homologous to the a, c, and d subunits in eukaryotic V-ATPases, respectively, and, for clarity, the eukaryotic subunit names are used here. With this convention, the T. thermophilus V/A-ATPase contains subunits A 3 B 3 DE 2 FG 2 ac 12 d whereas the eukaryot...

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“…O cristal da bacteriorodopsina mostrou que esta proteína possui sete segmentos transmembranares a-helicoidais. Dessa forma, a bacteriorodopsina foi utilizada como molde para modelos estruturais tridimensionais para os GPCRs (7)(8)(9)(10).…”

Section: Estrutura Dos Gpcrs Dafamília Da Rodopsinaunclassified

“…(23) concluiram que as TMs formavam a-hélices regulares. No entanto, a estrutura cristalina da rodopsina revelou que as TMs não formam a-hélices regulares, na verdade contém segmentos com hélices 3 10 ou 1t (24). Visiers et aI.…”

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Estudos conformacionais de seqüências hidrofóbicas de domínios de receptores acoplados a proteínas G (GPCR) e da proteína G. Um estudo de CD e espectroscopia de fluorescência

Casallanovo¹

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AgradecimentosAo pessoal do laboratório, Salay, Felipe, Myriam, Fábio Dyszy, Tatiana e Marcelo, obrigado pela paciência e pela ajuda. À Aninha, obrigado pelos papos, discussões e pelo apoio.Ao Carlos Àlvares, que me ajudou muito nos momentos finais.Ao pessoal que passou pelo LBE, Raquel, Berê, Noboru, Roberto Salinas, Goretti, Thelma e Mercedes.Ã Renata Fischer, pela amizade.Ao Claúdio S. Shida, que me ajudou muito em vários momentos, obrigado pelos conselhos e pela amizade.Aos meus amigos Eroc, Paulo, Luís Mayer e Luiz, obrigado pelo apoio e por me agüentar nos momentos mais dificeis.À Lua, que é uma pessoa que eu gosto muito e com a qual tive uma ótima amizade desde o primeiro dia em que entrei no laboratório como aluno de iniciação científica. Obrigado pelos conselhos e pelos momentos de alegria. À Dra. Shirley, que é uma pessoa muito especial. Poucas pessoas sabem contar estórias e atrair a admiração dos outros como você. Com você aprendi muito, sempre admirei sua postura e inteligência. Você também soube ser muito compreensiva nos momentos mais dificeis.À Fapesp e ao CNPq, obrigado pelo apoio finaceiro.o. Índice 1 Índice Lista de abreviações .................................................................................................................................... iv Resumo ........................................................................................................................................................ v O peptídeo estudado mostrou-se muito sensível à força iônica, pH e TFE, observando-se mudança de estrutura ao acaso para a-hélice em alguns pHs e na presença de TFE e para folha ~ com o aumento da força iônica.Na presença de detergentes, observou-se que o peptídeo era capaz de ligar-se tanto a interfaces com carga líquida zero (HPS e LPC) quanto com carga líquida negativa. Observou-se também que o CG tem maior afinidade por LPC do que por HPS.O estudo do CG em diferentes condições forneceu subsídios para investigannos a interação deste fragmento com regiões do receptor A TIA de angiotensina 11 que estão envolvidas com a ativação da proteína G. analog displayed the highest propensity to acquire a-helical conformation in the presence of TFE and in aqueous solution.In the presence of detergents we observed that the peptides were able to bind to different interfaces, especially negatively charged ones. In the presence of phospholipid membranes, all peptides displayed p-sheet conformation.In order to study the effect of aggregation, we performed experiments in the presence of denaturing agents such as urea and as a function of temperature. Even in the presence of high urea concentrations and at higher temperatures, the fragments remained aggregated. This result led us to another approach, where peptide films were hydrated in the presence of detergents. Using this methodology it was observed that the fragments were less aggregated, indicating that under adequate conditions the peptides tend to adopt a-helical conformation. In summary, it was possible to observe experimentall...

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Modeling of transmembrane seven helix bundles

Cited by 102 publications

References 0 publications

Three‐Dimensional Structure of the Highly Conserved Seventh Transmembrane Domain of G‐Protein‐Coupled Receptors

Three‐Dimensional Structure of the Highly Conserved Seventh Transmembrane Domain of G‐Protein‐Coupled Receptors

Models for the a subunits of the Thermus thermophilus V/A-ATPase and Saccharomyces cerevisiae V-ATPase enzymes by cryo-EM and evolutionary covariance

Estudos conformacionais de seqüências hidrofóbicas de domínios de receptores acoplados a proteínas G (GPCR) e da proteína G. Um estudo de CD e espectroscopia de fluorescência

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