SFB 594:  Molecular Machines in Protein Folding and Protein Transport

• Subject Area: Biology ; Medicine
• Term: from 2001 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5484884

Molecular machines perform complex multi-step operations on a molecular level and by that produce, degrade, or reconfigure molecular substrates in a variety of ways. They are themselves complex structures consisting of a number of subunits. The aim of this collaborative research centre is to elucidate the basic structures and mechanisms of molecular machines which influence a protein’s folding state and thereby control further reactions: de novo protein folding, refolding of stress denatured proteins, degradation, and protein translocation. Proteins depend on helper proteins (chaperones) in order to adopt their correct folding state; the degradation of native proteins requires ATPases for unfolding; and translocation of proteins is mediated by complex translocases. One focus is on chaperone-mediated folding of proteins (GroEL/GroES, Hsp90), disintegration of protein aggregates (Hsp104, Hsp70/Hsp40), the archaeal chaperone VAT, and small heat shock proteins (Hsp12, Hsp26, Hsp42). Furthermore, the molecular mechanisms of the ATPase ISWI in altering chromatin structure and of complex proteases (20S Proteasome, HsIV/HSIU) are addressed. Another focus is to study molecular machines which transport proteins across membranes. It is planned to investigate the structural and molecular mechanisms of protein translocase complexes of bacteria (SecYEG, and Typ III protein secretion system), mitochondria (TOM, TIM22, TIM23, and OXA), and of chloroplasts (TOC, TIC and Albino 3).

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Mechanisms of chaperonins and down-stream factors in assisted proetin folding and assembly (Project Heads Hartl, Franz-Ulrich ;  Hayer-Hartl, Manajit )
• A02 - Structural and functional analysis of the Hsp90 chaperone complex (Project Head Buchner, Johannes )
• A03 - Funktionsanalyse des molekularen Chaperons Hsp104 (Project Head Walter, Stefan )
• A04 - Structure and funktion of VAT, the archaeal homologue of Cdc48 and p97 (Project Heads Baumeister, Wolfgang ;  Kessler, Horst ;  Peters, Jürgen )
• A05 - Structural and functional analysis of small heat shock proteins (Project Heads Buchner, Johannes ;  Haslbeck, Martin )
• A06 - Remodelling of complex chromatin by the ATP-dependent nucleosome assembly and remodelling factor (ACF) (Project Head Becker, Peter Burkhard )
• A07 - The 20S Proteasome: Mechanisms of assembly and substrate translocation (Project Head Baumeister, Wolfgang )
• A8 - HsiVU und die Proteasom assoziierten ATPasen (Project Heads Groll, Michael ;  Huber, Robert )
• A09 - Regulation, Inhibition and Dynamics of Molecular Chaperones and their Complexes (Project Head Kessler, Horst )
• A10 - Function of the Cdc48 segregase and its co-factors (Project Head Jentsch, Stefan )
• A11 - Structural and functional characterization of complex protein modules involved in regulation of proteasomal activity (Project Head Groll, Michael )
• B01 - Structural analyses on bacterial preprotein translocase and small heat shock proteins (Project Head Weinkauf, Sevil )
• B2 - Die Präproteintranslokase der mitochondrialen Außenmembran: Transport von Proteinen durch die Nanoporen des TOM Komplexes (Project Head Nußberger, Stephan Boris )
• B03 - Protein translocases inolved in the sorting of proteins into the innermembrane of mitochondria (Project Head Neupert, Walter )
• B4 - Der TIM22-54 Komplex: Proteintranslokations- und Membraninsertionsmaschine für polytope Proteine der Innenmembran in Mitochondrien (Project Heads Hell, Kai ;  Prokisch, Holger )
• B05 - Die OXA1-Proteininsertionsmaschine der Mitochondrien (Project Head Herrmann, Johannes M. )
• B06 - Molecular analysis of the type 3 protein secretion/translocation System of Yersinia enterocolitica (Project Head Heesemann, Jürgen )
• B08 - Organisation und Biogenese von supramolekularen Maschinen in der Innenmembran von Mitochondrien (Project Head Reichert, Andreas )
• B09 - Identifikation, Isolation und Aharakterisierung des Proteinexport-Komplexes Albino3 der Thylakoidmembran höherer Pflanzen (Project Head Eichacker, Lutz )
• B10 - Function and regulation of the protein translocon at the inner envelope of Chloroplasts (Project Head Soll, Jürgen )
• B11 - Strukturelle und Funktionelle Analyse des Translokationskomplexes der äußeren Hüllmembran von Chloroplasten (Project Head Schleiff, Enrico )
• B12 - Molecular structure and function of the preprotein translocase of the outer membrane of mitochondria (Project Head Rapaport, Doron )
• B13 - The mitochondrial import motor of preproteins (Project Head Hell, Kai )
• B14 - Crystal structure analysis of the mitochondrial TOM-Protein-Translocase-Complex (Project Heads Groll, Michael ;  Neupert, Walter )
• B15 - Visualization of the ribosometranslocon complex: nascent transmembrane domains in the ribosomal tunnnel and the active translocon in the membrane (Project Head Beckmann, Roland )
• B16 - Timl 7/22/23 homologs in chloroplasts: function and significance in protein Transport (Project Heads Bölter, Bettina ;  Soll, Jürgen )
• B17 - The functional architecture of the ribosome-NAC complex and its role in protein targeting (Project Heads Beatrix, Birgitta ;  Beckmann, Roland )
• B18 - Structural and functional dissection of the mitochondrial TIM23 preprotein translocase (Project Head Mokranjac, Dejana )
• B19 - Structural analysis and dynamics of molecular recognition in peroxisomal import (Project Head Sattler, Michael )
• Z01 - Central tasks of the Collaborative Research Center (Project Head Neupert, Walter )
• Z02 - Protein Analysis Unit / Core Facility (Project Head Imhof, Axel )

• Applicant Institution: Ludwig-Maximilians-Universität München
• Participating University: Technische Universität München (TUM)
• Participating Institution: Max-Planck-Institut für Biochemie (MPIB)
• Spokesperson: Professor Dr. Roland Beckmann