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Revealing conformational substates of lipidated N-Ras protein by pressure modulation [Biophysics and Computational Biology] (2012)

Kapoor, S., Triola, G., Vetter, I. R., Erlkamp, M., Waldmann, H., Winter, R.

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences

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Publikationsdatum: 2012-01-12

Beschreibung: Regulation of protein function is often linked to a conformational switch triggered by chemical or physical signals. To evaluate such conformational changes and to elucidate the underlying molecular mechanisms of subsequent protein function, experimental identification of conformational substates and characterization of conformational equilibria are mandatory. We apply pressure modulation in combination with FTIR spectroscopy to reveal equilibria between spectroscopically resolved substates of the lipidated signaling protein N-Ras. Pressure has the advantage that its thermodynamic conjugate is volume, a parameter that is directly related to structure. The conformational dynamics of N-Ras in its different nucleotide binding states in the absence and presence of a model biomembrane was probed by pressure perturbation. We show that not only nucleotide binding but also the presence of the membrane has a drastic effect on the conformational dynamics and selection of conformational substates of the protein, and a new substate appearing upon membrane binding could be uncovered. Population of this new substate is accompanied by structural reorientations of the G domain, as also indicated by complementary ATR-FTIR and IRRAS measurements. These findings thus illustrate that the membrane controls signaling conformations by acting as an effective interaction partner, which has consequences for the G-domain orientation of membrane-associated N-Ras, which in turn is known to be critical for its effector and modulator interactions. Finally, these results provide insights into the influence of pressure on Ras-controlled signaling events in organisms living under extreme environmental conditions as they are encountered in the deep sea where pressures reach the kbar range.

Print ISSN: 0027-8424

Digitale ISSN: 1091-6490

Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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2

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Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB (2013)

Emerich Mihai Gazdag; Alexandra Streller; Ina Haneburger; Hubert Hilbi; Ingrid R Vetter; Roger S Goody; Aymelt Itzen

Nature Publishing Group (NPG)

In: EMBO Reports

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Publikationsdatum: 2013-02-02

Beschreibung: EMBO Reports 14, 199 (2013). doi:10.1038/embor.2012.211 Authors: Emerich Mihai Gazdag, Alexandra Streller, Ina Haneburger, Hubert Hilbi, Ingrid R Vetter, Roger S Goody & Aymelt Itzen

Print ISSN: 1469-221X

Digitale ISSN: 1469-3178

Thema: Biologie , Medizin

Publiziert von Nature Publishing Group (NPG) im Namen von The European Molecular Biology Organization (EMBO).

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3

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A Toxoplasma Target for Acyl-protein Thioesterase Inhibitors [Membrane Biology] (2013)

Kemp, L. E., Rusch, M., Adibekian, A., Bullen, H. E., Graindorge, A., Freymond, C., Rottmann, M., Braun-Breton, C., Baumeister, S., Porfetye, A. T., Vetter, I. R., Hedberg, C., Soldati-Favre, D.

The American Society for Biochemistry and Molecular Biology (ASBMB)

In: Journal of Biological Chemistry

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Publikationsdatum: 2013-09-21

Beschreibung: In eukaryotic organisms, cysteine palmitoylation is an important reversible modification that impacts protein targeting, folding, stability, and interactions with partners. Evidence suggests that protein palmitoylation contributes to key biological processes in Apicomplexa with the recent palmitome of the malaria parasite Plasmodium falciparum reporting over 400 substrates that are modified with palmitate by a broad range of protein S-acyl transferases. Dynamic palmitoylation cycles require the action of an acyl-protein thioesterase (APT) that cleaves palmitate from substrates and conveys reversibility to this posttranslational modification. In this work, we identified candidates for APT activity in Toxoplasma gondii. Treatment of parasites with low micromolar concentrations of β-lactone- or triazole urea-based inhibitors that target human APT1 showed varied detrimental effects at multiple steps of the parasite lytic cycle. The use of an activity-based probe in combination with these inhibitors revealed the existence of several serine hydrolases that are targeted by APT1 inhibitors. The active serine hydrolase, TgASH1, identified as the homologue closest to human APT1 and APT2, was characterized further. Biochemical analysis of TgASH1 indicated that this enzyme cleaves substrates with a specificity similar to APTs, and homology modeling points toward an APT-like enzyme. TgASH1 is dispensable for parasite survival, which indicates that the severe effects observed with the β-lactone inhibitors are caused by the inhibition of non-TgASH1 targets. Other ASH candidates for APT activity were functionally characterized, and one of them was found to be resistant to gene disruption due to the potential essential nature of the protein.

Print ISSN: 0021-9258

Digitale ISSN: 1083-351X

Thema: Biologie , Chemie und Pharmazie

Publiziert von The American Society for Biochemistry and Molecular Biology (ASBMB)

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4

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Structure of human {alpha}TAT1 [Biochemistry] (2012)

Taschner, M., Vetter, M., Lorentzen, E.

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences

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Publikationsdatum: 2012-11-28

Beschreibung: Acetylation of lysine residues is an important posttranslational modification found in all domains of life. α-tubulin is specifically acetylated on lysine 40, a modification that serves to stabilize microtubules of axons and cilia. Whereas histone acetyltransferases have been extensively studied, there is no structural and mechanistic information available on α-tubulin...

Print ISSN: 0027-8424

Digitale ISSN: 1091-6490

Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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5

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Isolation and Structural and Pharmacological Characterization of α-Elapitoxin-Dpp2d, an Amidated Three Finger Toxin from Black Mamba Venom (2014)

Ching-I Anderson Wang, Timothy Reeks, Irina Vetter, Irene Vergara, Oleksiy Kovtun, Richard J. Lewis, Paul F. Alewood and Thomas Durek

American Chemical Society (ACS)

In: Biochemistry

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Publikationsdatum: 2014-06-06

Beschreibung: Biochemistry DOI: 10.1021/bi5004475

Print ISSN: 0006-2960

Digitale ISSN: 1520-4995

Thema: Biologie , Chemie und Pharmazie

Publiziert von American Chemical Society (ACS)

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6

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Yersinia pestis infection and laboratory conditions alter flea-associated bacterial communities (2012)

Ryan T Jones; Sara M Vetter; John Montenieiri; Jennifer Holmes; Scott A Bernhardt; Kenneth L Gage

Nature Publishing Group (NPG)

In: ISME Journal

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Publikationsdatum: 2012-12-19

Beschreibung: Yersinia pestis infection and laboratory conditions alter flea-associated bacterial communities The ISME Journal 7, 224 (January 2013). doi:10.1038/ismej.2012.95 Authors: Ryan T Jones, Sara M Vetter, John Montenieiri, Jennifer Holmes, Scott A Bernhardt & Kenneth L Gage

Schlagwort(e): Bartonellaexperimental infectionplague

Print ISSN: 1751-7362

Digitale ISSN: 1751-7370

Thema: Biologie

Publiziert von Nature Publishing Group (NPG) im Namen von The International Society for Microbial Ecology (ISME).

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7

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Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119 (2012)

Shehab A Ismail; Yong-Xiang Chen; Mandy Miertzschke; Ingrid R Vetter; Carolin Koerner; Alfred Wittinghofer

Nature Publishing Group (NPG)

In: EMBO Journal

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Publikationsdatum: 2012-10-18

Beschreibung: The EMBO Journal 31, 4085 (2012). doi:10.1038/emboj.2012.257 Authors: Shehab A Ismail, Yong-Xiang Chen, Mandy Miertzschke, Ingrid R Vetter, Carolin Koerner & Alfred Wittinghofer Access to the ciliary membrane for trans-membrane or membrane-associated proteins is a regulated process. Previously, we have shown that the closely homologous small G proteins Arl2 and Arl3 allosterically regulate prenylated cargo release from PDEδ. UNC119/HRG4 is responsible for ciliary delivery of myristoylated cargo. Here,

Schlagwort(e): Arfsciliaprotein traffickingreleasing factorssmall G proteins

Print ISSN: 0261-4189

Digitale ISSN: 1460-2075

Thema: Biologie , Medizin

Publiziert von Nature Publishing Group (NPG) im Namen von The European Molecular Biology Organization (EMBO).

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8

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Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling (2012)

Irina Vetter; Filip Touska; Andreas Hess; Rachel Hinsbey; Simon Sattler; Angelika Lampert; Marina Sergejeva; Anastasia Sharov; Lindon S Collins; Mirjam Eberhardt; Matthias Engel; Peter J Cabot; John N Wood; Viktorie VlachováPeter W Reeh; Richard J Lewis; Katharina Zimmermann

Nature Publishing Group (NPG)

In: EMBO Journal

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Publikationsdatum: 2012-10-04

Beschreibung: Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling The EMBO Journal 31, 3795 (2012). doi:10.1038/emboj.2012.207 Authors: Irina Vetter, Filip Touska, Andreas Hess, Rachel Hinsbey, Simon Sattler, Angelika Lampert, Marina Sergejeva, Anastasia Sharov, Lindon S Collins, Mirjam Eberhardt, Matthias Engel, Peter J Cabot, John N Wood, Viktorie Vlachová, Peter W Reeh, Richard J Lewis & Katharina Zimmermann Ciguatoxins are sodium channel activator toxins that cause ciguatera, the most common form of ichthyosarcotoxism, which presents with peripheral sensory disturbances, including the pathognomonic symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling. We show that

Schlagwort(e): ciguatoxincold allodyniaNavnociceptorTRPA1

Print ISSN: 0261-4189

Digitale ISSN: 1460-2075

Thema: Biologie , Medizin

Publiziert von Nature Publishing Group (NPG) im Namen von The European Molecular Biology Organization (EMBO).

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Actions of {phiv}-LITX-Lw1a on ryanodine receptors [Biochemistry] (2013)

Smith, J. J., Vetter, I., Lewis, R. J., Peigneur, S., Tytgat, J., Lam, A., Gallant, E. M., Beard, N. A., Alewood, P. F., Dulhunty, A. F.

National Academy of Sciences

In: PNAS - Proceedings of the National Academy of Sciences

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Publikationsdatum: 2013-05-29

Beschreibung: We recently reported the isolation of a scorpion toxin named U1-liotoxin-Lw1a (U1-LITX-Lw1a) that adopts an unusual 3D fold termed the disulfide-directed hairpin (DDH) motif, which is the proposed evolutionary structural precursor of the three-disulfide-containing inhibitor cystine knot (ICK) motif found widely in animals and plants. Here we reveal that U1-LITX-Lw1a...

Print ISSN: 0027-8424

Digitale ISSN: 1091-6490

Thema: Biologie , Medizin , Allgemeine Naturwissenschaft

Publiziert von National Academy of Sciences

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The interplay between RPGR, PDEδ and Arl2/3 regulate the ciliary targeting of farnesylated cargo (2013)

Denise Wätzlich; Ingrid Vetter; Katja Gotthardt; Mandy Miertzschke; Yong-Xiang Chen; Alfred Wittinghofer; Shehab Ismail

Nature Publishing Group (NPG)

In: EMBO Reports

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Publikationsdatum: 2013-05-03

Beschreibung: EMBO Reports 14, 465 (2013). doi:10.1038/embor.2013.37 Authors: Denise Wätzlich, Ingrid Vetter, Katja Gotthardt, Mandy Miertzschke, Yong-Xiang Chen, Alfred Wittinghofer & Shehab Ismail Defects in primary cilia result in human diseases known as ciliopathies. The retinitis pigmentosa GTPase regulator (RPGR), mutated in the most severe form of the eye disease, is located at the transition zone of the ciliary organelle. The RPGR-interacting partner PDEδ is involved in trafficking

Schlagwort(e): ciliary traffickingretinitis pigmentosaRPGRArl2/Arl3PDEδ

Print ISSN: 1469-221X

Digitale ISSN: 1469-3178

Thema: Biologie , Medizin

Publiziert von Nature Publishing Group (NPG) im Namen von The European Molecular Biology Organization (EMBO).

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