9QWQ

Human vault protein - committed conformation

This is a non-PDB format compatible entry.

Summary for 9QWQ

• Entry DOI: 10.2210/pdb9qwq/pdb
• Related: 9QW9
• EMDB information: 53423
• Descriptor: Major vault protein (1 entity in total)
• Functional Keywords: vault protein, vault, mvp, cytosolic protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 78
• Total formula weight: 7757315.75

Authors

Lapenta, F.,Marechal, N.,Durand, A.,Aupic, J.,Cassetta, A. (deposition date: 2025-04-15, release date: 2026-05-06, Last modification date: 2026-05-13)

Primary citation

Lapenta, F.,Palacio-Rodriguez, K.,Cruz-Leon, S.,Marrancone, S.,Aupic, J.,Marechal, N.,Durand, A.,Moussaoui, D.,Covaceuszach, S.,Gangupam, B.,D'Ercole, C.,Parra, C.,Cotugno, D.,Tomaino, G.,Tortora, P.,de Marco, A.,Cassetta, A.,Magistrato, A.,Hummer, G.
Structural flexibility of the human vault particle revealed by high-resolution cryo-EM and molecular dynamics simulations.
Nat Commun, 2026

PubMed Abstract: Vaults are massive ribonucleoprotein complexes, highly conserved and abundant in eukaryotic cells, yet with unclear function. Their thin-walled barrel-shape architecture is composed of two symmetrical, antiparallel half-shells, each containing 39 copies of the major vault protein (MVP). The spacious lumen of the vault suggests a role in cellular transport. Although vaults are thought to undergo conformational changes to facilitate cargo exchange, the molecular basis for their inherent flexibility remains unknown. Here, we integrate cryogenic electron microscopy (cryo-EM) and multi-scale molecular dynamics (MD) simulations to reveal the structural determinants of the human vault particle's flexibility. Cryo-EM identified two high-resolution alternative conformational states: a symmetric and an asymmetric structure, pointing to the vault shell's structural plasticity. MD simulations of these conformations revealed that these structures are flexible and exhibit breathing-like motions, and porous solvent-exposed surfaces. Mutagenesis disrupting persistent MD-identified inter-half contacts reduced full MVP shell assembly, confirming the functional relevance of these flexibility determinants. Together, these findings establish the molecular basis for the human vault particle's conformational plasticity.

PubMed: 42069735
DOI: 10.1038/s41467-026-72674-4

Experimental method

ELECTRON MICROSCOPY (4.45 Å)