Εξειδίκευση τύπου :	Άρθρο σε περιοδικό τύπο
Τίτλος:	Structural analysis of an endogenous 4-megadalton succinyl-CoA-generating metabolon
Δημιουργός/Συγγραφέας:	Skalidis, Ioannis Kyrilis, Fotis L Tüting, Christian Hamdi, Farzad Träger, Toni K Belapure, Jaydeep Hause, Gerd Fratini, Marta O'Reilly, Francis J Heilmann, Ingo Rappsilber, Juri [EL] Καστρίτης, Παναγιώτης[EN] Kastritis, Panagiotis
Ημερομηνία:	2023-05-22
Γλώσσα:	Αγγλικά
ISSN:	2399-3642
DOI:	10.1038/s42003-023-04885-0
Άλλο:	37217784
Περίληψη:	The oxoglutarate dehydrogenase complex (OGDHc) participates in the tricarboxylic acid cycle and, in a multi-step reaction, decarboxylates α-ketoglutarate, transfers succinyl to CoA, and reduces NAD+. Due to its pivotal role in metabolism, OGDHc enzymatic components have been studied in isolation; however, their interactions within the endogenous OGDHc remain elusive. Here, we discern the organization of a thermophilic, eukaryotic, native OGDHc in its active state. By combining biochemical, biophysical, and bioinformatic methods, we resolve its composition, 3D architecture, and molecular function at 3.35 Å resolution. We further report the high-resolution cryo-EM structure of the OGDHc core (E2o), which displays various structural adaptations. These include hydrogen bonding patterns confining interactions of OGDHc participating enzymes (E1o-E2o-E3), electrostatic tunneling that drives inter-subunit communication, and the presence of a flexible subunit (E3BPo), connecting E2o and E3. This multi-scale analysis of a succinyl-CoA-producing native cell extract provides a blueprint for structure-function studies of complex mixtures of medical and biotechnological value.
Τίτλος πηγής δημοσίευσης:	Communications biology
Τόμος/Κεφάλαιο:	6
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Βιοχημεία[EN] Biochemistry [EL] Δομική Βιολογία[EN] Structural Biology [EL] Βιοπληροφορική[EN] Bioinformatics [EL] Φασματοσκοπία[EN] Spectroscopy
Λέξεις-Κλειδιά:	Acyl Coenzyme A Cytoplasm Ketoglutarate Dehydrogenase Complex Citric Acid Cycle
EU Grant:	Projekt DEAL
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://www.nature.com/articles/s42003-023-04885-0
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο