8QL1

Crystal structure of the human MDN1-MIDAS/NLE1-UBL complex

Summary for 8QL1

• Entry DOI: 10.2210/pdb8ql1/pdb
• Descriptor: NDE1, Notchless protein homolog 1, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: aaa+ atpase, metal ion dependent adhesion site (midas), ubiquitin-like domain (ubl), pre-60s biogenesis, ribosome
• Biological source: Homo sapiens; More
• Total number of polymer chains: 8
• Total formula weight: 172477.12

Authors

Wild, K.,Fiorentino, F.,Hurt, E.,Sinning, I. (deposition date: 2023-09-19, release date: 2025-04-09, Last modification date: 2025-04-30)

Primary citation

Fiorentino, F.,Thoms, M.,Wild, K.,Denk, T.,Cheng, J.,Zeman, J.,Sinning, I.,Hurt, E.,Beckmann, R.
Highly conserved ribosome biogenesis pathways between human and yeast revealed by the MDN1-NLE1 interaction and NLE1 containing pre-60S subunits.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: The assembly of ribosomal subunits, primarily occurring in the nucleolar and nuclear compartments, is a highly complex process crucial for cellular function. This study reveals the conservation of ribosome biogenesis between yeast and humans, illustrated by the structural similarities of ribosomal subunit intermediates. By using X-ray crystallography and cryo-EM, the interaction between the human AAA+ ATPase MDN1 and the 60S assembly factor NLE1 is compared with the yeast homologs Rea1 and Rsa4. The MDN1-MIDAS and NLE1-Ubl complex structure at 2.3 Å resolution mirrors the highly conserved interaction patterns observed in yeast. Moreover, human pre-60S intermediates bound to the dominant negative NLE1-E85A mutant revealed at 2.8 Å resolution an architecture that largely matched the equivalent yeast structures. Conformation of rRNA, assembly factors and their interaction networks are highly conserved. Additionally, novel human pre-60S intermediates with a non-rotated 5S RNP and processed ITS2/foot structure but incomplete intersubunit surface were identified to be similar to counterparts observed in yeast. These findings confirm that the MDN1-NLE1-driven transition phase of the 60S assembly is essentially identical, supporting the idea that ribosome biogenesis is a highly conserved process across eukaryotic cells, employing an evolutionary preservation of ribosomal assembly mechanisms.

PubMed: 40207627
DOI: 10.1093/nar/gkaf255

Experimental method

X-RAY DIFFRACTION (2.3 Å)