Sah-Teli, S. K., Pinkas, M., Hynönen, M. J., Butcher, S. J., Wierenga, R. K., Novacek, J., & Venkatesan, R. (2023). Structural basis for different membrane-binding properties of E. coli anaerobic and human mitochondrial β-oxidation trifunctional enzymes. Structure, 31(7), 812-825.e6. https://doi.org/10.1016/j.str.2023.04.011, Structure, 2023, ISSN 0969-2126, https://doi.org/10.1016/j.str.2023.04.011
Structural basis for different membrane-binding properties of E. coli anaerobic and human mitochondrial β-oxidation trifunctional enzymes
|Author:||Sah-Teli, Shiv K.1; Pinkas, Matyas2; Hynönen, Mikko J.1;|
1Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90220 Oulu, Finland
2CEITEC Masaryk University, Kamenice 5, 62500 Brno, Czech Republic
3Molecular & Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences & Helsinki Institute of Life Science-Institute of Biotechnology, University of Helsinki, 00790 Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 6.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2023052948993
|Publish Date:|| 2023-05-29
Facultative anaerobic bacteria such as Escherichia coli have two α₂β₂ heterotetrameric trifunctional enzymes (TFE), catalyzing the last three steps of the β-oxidation cycle: soluble aerobic TFE (EcTFE) and membrane-associated anaerobic TFE (anEcTFE), closely related to the human mitochondrial TFE (HsTFE). The cryo-EM structure of anEcTFE and crystal structures of anEcTFE-α show that the overall assembly of anEcTFE and HsTFE is similar. However, their membrane-binding properties differ considerably. The shorter A5-H7 and H8 regions of anEcTFE-α result in weaker α-β as well as α-membrane interactions, respectively. The protruding H-H region of anEcTFE-β is therefore more critical for membrane-association. Mutational studies also show that this region is important for the stability of the anEcTFE-β dimer and anEcTFE heterotetramer. The fatty acyl tail binding tunnel of the anEcTFE-α hydratase domain, as in HsTFE-α, is wider than in EcTFE-α, accommodating longer fatty acyl tails, in good agreement with their respective substrate specificities.
|Pages:||812 - 825|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
We acknowledge the support from the beam line scientists at Diamond Light Source (I24), UK, PETRA-III (P14), Germany, and ESRF (BM29), France. We acknowledge the support from the Biocenter Oulu Structural Biology Core Facility, the HislLIFE Cryo-EM Unit, University of Helsinki (members of Instruct Centrer FI, FINStruct, and Biocenter Finland). We thank Dr. Werner Schmitz, University of Würzburg, Germany, for providing the 2E-decenoyl-CoA substrate. The work was supported by funding from the Academy of Finland (grant nos. 293369, 289024, and 319194), the Magnus Ehrnrooth Foundation and the North Ostrobothnia Regional Fund of the Finnish Cultural Foundation. We acknowledge the cryoelectron microscopy core facility of CIISB, Instruct Centre CZ supported by MEYS CR (LM2023042) and European Regional Development Fund-Project “UP CIISB” (no. CZ.02.1.01/0.0/0.0/18_046/0015974), Instruct-ERIC (PID 11892), and iNEXT-Discovery (project no. 871037), as well as iNEXT (project no. 653706), funded by the Horizon 2020 program of the European Commission.
|EU Grant Number:||
(653706) iNEXT - Infrastructure for NMR, EM and X-rays for translational research
|Academy of Finland Grant Number:||
293369 (Academy of Finland Funding decision)
289024 (Academy of Finland Funding decision)
319194 (Academy of Finland Funding decision)
© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (https://doi.org/10.1016/j.str.2023.04.011).