Selective ribosome profiling and biochemistry studies on the co-translational protein folding and assembly in eukaryotic protein synthesis

Projektinformationen

srpabsotcpfaaieps

ID Finanzhilfevereinbarung: 753530

DOI 10.3030/753530

Projekt abgeschlossen

EK-Unterschriftsdatum 20 März 2017

Startdatum 1 Mai 2018

Enddatum 1 September 2023

Finanziert unter

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Gesamtkosten € 171 460,80

EU-Beitrag € 171 460,80

Koordiniert durch

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG
Germany

Ziel

Biological activity of cells depends on timely production of natively folded proteins by powerful translation and folding machineries. At a critical regulatory intersection of translation and folding, ribosomes act as integration hubs coordinating chaperone, enzyme and membrane targeting factor activity, influencing folding. Final assembly of proteins into oligomeric complexes however, has long been considered post-translational and dependent on random collision of fully synthesized diffusing subunits. In a shift of paradigm, recent evidence from the Bukau laboratory now suggests that in bacteria, assembly initiates co-translationally assisted by chaperones, and gene organization into operons drives co-localized translation of complex subunits that impacts efficiency of assembly. Fundamental differences in eukaryotes such as rarity of operons and differing chaperone constellations imply a widely different folding and assembly biology, which remains largely unexplored. The selective ribosome profiling (SeRP) method, developed by the Bukau lab, now allows ground breaking identification and definition of dynamic interactions of nascent chains, at near-residue resolution. Using SeRP with supporting biochemistry, I will unravel the nascent chain molecular biology underpinning protein folding and assembly in yeast, Saccharomyces cerevisiae, a powerful model for studying the fundamental aspects of this biology. Specifically, I will establish (1) basic features and prevalence of co-translational protein assembly, (2) how chaperones guide co-translational protein folding to affect assembly. Subunit interaction profiles complemented by chaperone interaction profiles, will expose the timing and interplay of protein folding and assembly steps linked to protein synthesis, establishing a detailed conceptually new biology of complex assembly in eukaryotes.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › microbiology › bacteriology
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › protein folding
• natural sciences › biological sciences › biochemistry › biomolecules › proteins › enzymes
• natural sciences › biological sciences › molecular biology

Schlüsselbegriffe

• yeast
• ribosomes
• protein folding
• chaperones
• co-translation protein complex assembly

Programm/Programme

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility

Thema/Themen

• MSCA-IF-2016 - Individual Fellowships

Aufforderung zur Vorschlagseinreichung

H2020-MSCA-IF-2016

Finanzierungsplan

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Koordinator

RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG

• Netto-EU-Beitrag: € 171 460,80
• Adresse: SEMINARSTRASSE 2 ; 69117 Heidelberg ; Deutschland
• Region: Baden-Württemberg › Karlsruhe › Heidelberg, Stadtkreis
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 171 460,80