8BGU

human MDM2-5S RNP

Summary for 8BGU

• Entry DOI: 10.2210/pdb8bgu/pdb
• EMDB information: 16036
• Descriptor: E3 ubiquitin-protein ligase Mdm2, 5S rRNA, 60S ribosomal protein L5, ... (5 entities in total)
• Functional Keywords: 5s rnp, mdm2, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 149025.53

Authors

Castillo, N.,Thoms, M.,Flemming, D.,Hammaren, H.M.,Buschauer, R.,Ameismeier, M.,Bassler, J.,Beck, M.,Beckmann, R.,Hurt, E. (deposition date: 2022-10-28, release date: 2023-06-14, Last modification date: 2023-08-30)

Primary citation

Castillo Duque de Estrada, N.M.,Thoms, M.,Flemming, D.,Hammaren, H.M.,Buschauer, R.,Ameismeier, M.,Bassler, J.,Beck, M.,Beckmann, R.,Hurt, E.
Structure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2-p53 pathways.
Nat.Struct.Mol.Biol., 30:1119-1131, 2023

PubMed Abstract: The 5S ribonucleoprotein (RNP) is assembled from its three components (5S rRNA, Rpl5/uL18 and Rpl11/uL5) before being incorporated into the pre-60S subunit. However, when ribosome synthesis is disturbed, a free 5S RNP can enter the MDM2-p53 pathway to regulate cell cycle and apoptotic signaling. Here we reconstitute and determine the cryo-electron microscopy structure of the conserved hexameric 5S RNP with fungal or human factors. This reveals how the nascent 5S rRNA associates with the initial nuclear import complex Syo1-uL18-uL5 and, upon further recruitment of the nucleolar factors Rpf2 and Rrs1, develops into the 5S RNP precursor that can assemble into the pre-ribosome. In addition, we elucidate the structure of another 5S RNP intermediate, carrying the human ubiquitin ligase Mdm2, which unravels how this enzyme can be sequestered from its target substrate p53. Our data provide molecular insight into how the 5S RNP can mediate between ribosome biogenesis and cell proliferation.

PubMed: 37291423
DOI: 10.1038/s41594-023-01006-7

Experimental method

ELECTRON MICROSCOPY (4.1 Å)