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Kristallographische Studien an eukaryotischen Translationsinitiationsfaktoren und Komponenten der bakteriellen Proteinabbaumaschinerie

English title Crystallographic studies on eukaryotic translation initiation factors and on components of the eubacterial protein degradation machinery
Applicant Baumann Ulrich
Number 108262
Funding scheme Project funding (Div. I-III)
Research institution Departement für Chemie, Biochemie und Pharmazie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Biophysics
Start/End 01.04.2005 - 31.03.2008
Approved amount 260'000.00
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Keywords (5)

x-ray crystallography; metalloprotease; protein-turnover; eukaryotic translation initiation; methionine salvage pathway

Lay Summary (English)

Lead
Lay summary
The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog, named paraplegin, causes a form of spastic paraplegia. The first crystal structure of an FtsH construct which is active in ATPase and proteolytic assays has been determined at 2.44 A resolution in our laboratory. It reveals a hexameric molecule built by two stacked rings. One ring contains the proteolytic domains and forms a regular hexagon. The third zinc ligand had been miss-assigned to a glutamic acid before. We identified it correctly as an conserved aspartic acid. This finding classifies FtsH as a novel Asp-zincin. The other ring is formed by the AAA domains, which are all ADP loaded, and shows C2 symmetry only. The symmetry mismatch indicates a model for ATP-driven unfolding and translocation of the substrate polypeptide chain. This model could be largely confirmed by a recent crystal structure determination of a different crystal from at 2.7 A resolution.The carboxy-terminal domain of eukaryotic initiation factor 5 (eIF5) plays a central role in the formation of the multifactor complex (MFC), an important intermediate for the 43 S preinitiation complex assembly. The crystal structure of this domain has been determined by us at 1.8 A resolution. This domain of the protein is exclusively composed out of alpha-helices and is homologous to the carboxy-terminal domain of eIF2B-? (eIF2B?-CTD). Currently we are working on various complexes between different eIFs
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Associated projects

Number Title Start Funding scheme
67253 Crystallographic studies on eukaryotic translation initiation factors and on components of the eubacterial protein degradation machinery 01.04.2002 Project funding (Div. I-III)
120174 Crystallographic studies on eukaryotic translation initiation factors and on components of the eubacterial protein degradation machinery 01.04.2008 Project funding (Div. I-III)

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