9BW7

Human Vault Cage in complex with PARP4 and NAD+

9BW7 の概要

• エントリーDOI: 10.2210/pdb9bw7/pdb
• EMDBエントリー: 44957
• 分子名称: Major vault protein, Protein mono-ADP-ribosyltransferase PARP4, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: vault, vault cage, mvp, major vault protein, spfh, parp4, poly(adp-ribose) polymerase 4, mint, nad+, nad, poly(adp-ribose) polymerase, ribonucleoprotein, megadalton complex, tep1, vault rna, protein transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 585852.73

構造登録者

Lodwick, J.E.,Zhao, M. (登録日: 2024-05-20, 公開日: 2025-02-05, 最終更新日: 2025-08-06)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.9 Å)