Hunkeler, Moritz. Dynamic architecture of multi-domain carboxylases. 2015, PhD Thesis, University of Basel, Faculty of Science.
Restricted to Repository staff only until 1 January 2018.
Official URL: http://edoc.unibas.ch/diss/DissB_12004
One of the most prominent members of acyl-CoA carboxylases, acetyl-CoA carboxylase (ACC), catalyzes the conversion of acetyl-CoA to malonyl-CoA, the highly regulated committed step of fatty acid biosynthesis. Eukaryotic ACC is a giant multienzyme, encompassing all catalytic domains, the BCCP and a large non-catalytic central domain (CD) on one type of polypeptide chain. The overall structure of eukaryotic ACCs as well as the structure of the CD, which is unique to eukaryotic ACCs, and its role in ACC regulation, remain unknown.
This thesis provides a comprehensive characterization of the dynamic structure of fungal ACC by combining crystal structure determination, small-angle X-ray scattering (SAXS) and electron microscopy (EM). The crystal structure of yeast CD, accompanied by low-resolution data on larger fragments up to intact fungal ACCs, reveals that the CD acts as a multi-hinged link between the BC and CT domains. Phosphorylation has an impact on the dynamic architecture resulting in a unique “mechanical” control mechanism.
A novel class of prokaryotic multi-domain acyl-CoA carboxylases (YCCs) was discovered recently. They share the same domain organization with eukaryotic ACCs, but lack the CD. A hybrid model of the Deinococcus radiodurans YCC (Dra YCC), together with quantitative analysis of BC domain mobility, provides novel insights into active site structure, domain interactions and dynamic assembly of these prokaryotic multienzymes. The implications of our structural studies of yeast ACC and Dra YCC for multienzyme engineering are discussed.
In addition, the crystal structure and NMR analyses of the membrane-bound, dimeric bacterial extracellular foldase PrsA reveal a bowl-like crevice as the key structural element for binding and folding of unfolded proteins.
|Advisors:||Maier, Timm and Wahl, Markus C.|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Maier)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (175 Seiten)|
|Last Modified:||13 Feb 2017 07:34|
|Deposited On:||13 Feb 2017 07:34|
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