9BW5

Human Vault Cage

Summary for 9BW5

• Entry DOI: 10.2210/pdb9bw5/pdb
• EMDB information: 44953
• Descriptor: Major vault protein (1 entity in total)
• Functional Keywords: vault, vault cage, mvp, major vault protein, spfh, parp4, poly(adp-ribose)polymerase 4, poly(adp-ribose)polymerase, mint, ribonucleoprotein, megadalton complex, tep1, vault rna, protein transport
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 198905.53

Authors

Lodwick, J.E.,Zhao, M. (deposition date: 2024-05-20, release date: 2025-02-05, Last modification date: 2025-08-06)

Primary citation

Lodwick, J.E.,Shen, R.,Erramilli, S.,Xie, Y.,Roganowicz, K.,Ritchey, S.,Kossiakoff, A.A.,Zhao, M.
Structural insights into the roles of PARP4 and NAD + binding in the human vault cage.
Nat Commun, 16:6724-6724, 2025

PubMed Abstract: Vault is a massive ribonucleoprotein complex found across Eukaryota. The major vault protein (MVP) oligomerizes into an ovular cage, which contains several minor vault components (MVCs) and is thought to transport transiently bound "cargo" molecules. Vertebrate vaults house a poly (ADP-ribose) polymerase (known as PARP4 in humans), which is the only MVC with known enzymatic activity. Despite being discovered decades ago, the molecular basis for PARP4's interaction with MVP remains unclear. In this study, we determined the structure of the human vault cage in complex with PARP4 and its enzymatic substrate NAD. The structures reveal atomic-level details of the protein-binding interface, as well as unexpected binding sites for NAD and related nucleotides within the interior of the vault cage. In addition, proteomics data show that human vaults purified from wild-type and PARP4-depleted cells interact with distinct subsets of proteins. Our results thereby support a model in which PARP4's specific incorporation into the vault cage helps to regulate vault's selection of cargo and its subcellular localization. Further, PARP4's proximity to MVP's NAD-binding sites could support its enzymatic function within the vault.

PubMed: 40691181
DOI: 10.1038/s41467-025-61981-x

Experimental method

ELECTRON MICROSCOPY (3.3 Å)