8A0E

CryoEM structure of DHS-eIF5A1 complex

Summary for 8A0E

• Entry DOI: 10.2210/pdb8a0e/pdb
• Related: 6XXJ 7A6S 7A6T
• EMDB information: 15052
• Descriptor: Deoxyhypusine synthase, Eukaryotic translation initiation factor 5A, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (5 entities in total)
• Functional Keywords: hypusination, transferase, posttranslational modification
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 184545.81

Authors

Wator, E.,Wilk, P.,Biela, A.P.,Rawski, M.,Grudnik, P. (deposition date: 2022-05-27, release date: 2023-04-05, Last modification date: 2024-11-13)

Primary citation

Wator, E.,Wilk, P.,Biela, A.,Rawski, M.,Zak, K.M.,Steinchen, W.,Bange, G.,Glatt, S.,Grudnik, P.
Cryo-EM structure of human eIF5A-DHS complex reveals the molecular basis of hypusination-associated neurodegenerative disorders.
Nat Commun, 14:1698-1698, 2023

PubMed Abstract: Hypusination is a unique post-translational modification of the eukaryotic translation factor 5A (eIF5A) that is essential for overcoming ribosome stalling at polyproline sequence stretches. The initial step of hypusination, the formation of deoxyhypusine, is catalyzed by deoxyhypusine synthase (DHS), however, the molecular details of the DHS-mediated reaction remained elusive. Recently, patient-derived variants of DHS and eIF5A have been linked to rare neurodevelopmental disorders. Here, we present the cryo-EM structure of the human eIF5A-DHS complex at 2.8 Å resolution and a crystal structure of DHS trapped in the key reaction transition state. Furthermore, we show that disease-associated DHS variants influence the complex formation and hypusination efficiency. Hence, our work dissects the molecular details of the deoxyhypusine synthesis reaction and reveals how clinically-relevant mutations affect this crucial cellular process.

PubMed: 36973244
DOI: 10.1038/s41467-023-37305-2

Experimental method

ELECTRON MICROSCOPY (2.8 Å)