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Archiv-Übersicht     Angebot Nr. 12849

Angebotsdatum: 23. Mai 2018
Art der Stelle: Doktorarbeit / Diplomarbeit
Fachgebiet: Biologie > Molekularbiologie
Titel des Themas: Cryo-EM analysis of the co-translational machinery for protein folding and maturation

Institut: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Adresse:
Dr. rer. nat. Stefan Pfeffer
INF 282
69120 Heidelberg
Tel.:    Fax.:
Bundesland: Baden-Württemberg
Homepage: http://www.zmbh.uni-heidelberg.de/Pfeffer/default.shtml
E-Mail Kontakt: mail

Beschreibung: Co-translational folding and maturation of proteins require an intricate network of folding chaperones and processing enzymes that act on the growing nascent protein in a co-translational manner. Structural information on ribosome-nascent chain-chaperone complexes is sparse, because the involved interactions are mostly transient, labile and possibly highly flexible. This renders the involved assemblies inaccessible to classical reductionist structural biology approaches that rely on extensive biochemical purification and require conformationally homogenous particle populations for averaging. We consequently pursue a different approach and image these processes using cryo electron tomography (cryo-ET)-based strategies, which can reveal the three-dimensional arrangement of individual macromolecules even in crowded native microenvironments at molecular resolution and therefore render extensive biochemical purification unnecessary. This approach allows us to analyze the three-dimensional spatial distribution of ribosomes, chaperones and processing enzymes for individual native polysomal assemblies under conditions that preserve the labile and transient interactions governing co-translational protein folding and maturation. The central objective of this project will be to study defined polysomal assemblies engaged in the synthesis of model substrates. Cryo-ET approaches will be used to visualize these assemblies in both a non-cellular context and in sections of vitrified unperturbed cells obtained using focused ion beam (FIB) milling.
Methoden: High-resolution cryo electron microscopy and tomography approaches; advanced image processing; standard biochemical, molecular and cell biology methods
Anfangsdatum: 1. Juli 2018
Geschätzte Dauer: 3-4 years
Bezahlung:
Papers: Braunger K*, Pfeffer S*, Shrimal S, Gilmore R, Berninghausen O, Mandon EC, Becker T, Förster F, Beckmann R. Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum. Science 360, 215-219

Pfeffer, S., Dudek, J., Schaffer, M., Ng, B., Albert, S., Plitzko, J.M., Baumeister, W., Zimmermann, R., Freeze, H.H., Engel, B.D., Förster, F., 2017. Dissecting the molecular organization of the translocon-associated protein complex. Nat Commun 8, 14516.

Mahamid, J., Pfeffer, S., Schaffer, M., Villa, E., Danev, R., Cuellar, L.K., Förster, F., Hyman, A.A., Plitzko, J.M., Baumeister, W., 2016. Visualizing the molecular sociology at the HeLa cell nuclear periphery. Science 351, 969-972.

Pfeffer, S., Burbaum, L., Unverdorben, P., Pech, M., Chen, Y., Zimmermann, R., Beckmann, R., Förster, F., 2015. Structure of the native Sec61 protein-conducting channel. Nat Commun 6, 8403.

Pfeffer, S.*, Woellhaf, M.W.*, Herrmann, J.M., Förster, F., 2015. Organization of the mitochondrial translation machinery studied in situ by cryoelectron tomography. Nat Commun 6, 6019.

Pfeffer, S.*, Dudek, J.*, Gogala, M., Schorr, S., Linxweiler, J., Lang, S., Becker, T., Beckmann, R., Zimmermann, R., Förster, F., 2014. Structure of the mammalian oligosaccharyl-transferase complex in the native ER protein translocon. Nat Commun 5, 3072.

Pfeffer, S., Brandt, F., Hrabe, T., Lang, S., Eibauer, M., Zimmermann, R., Förster, F., 2012. Structure and 3D Arrangement of Endoplasmic Reticulum Membrane-Associated Ribosomes. Structure 20, 1508-1518.
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