| Structural highlights
Function
MVP_HUMAN Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport. Down-regulates INFG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases.[1] [2] [3]
Publication Abstract from PubMed
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 NAD (+) -binding pockets 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.
Structural Insights into the Roles of PARP4 and NAD (+) in the Human Vault Cage.,Lodwick JE, Shen R, Erramilli S, Xie Y, Roganowicz K, Kossiakoff AA, Zhao M bioRxiv [Preprint]. 2024 Jun 27:2024.06.27.601040. doi: , 10.1101/2024.06.27.601040. PMID:38979142[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kolli S, Zito CI, Mossink MH, Wiemer EA, Bennett AM. The major vault protein is a novel substrate for the tyrosine phosphatase SHP-2 and scaffold protein in epidermal growth factor signaling. J Biol Chem. 2004 Jul 9;279(28):29374-85. Epub 2004 May 7. PMID:15133037 doi:http://dx.doi.org/10.1074/jbc.M313955200
- ↑ Kim E, Lee S, Mian MF, Yun SU, Song M, Yi KS, Ryu SH, Suh PG. Crosstalk between Src and major vault protein in epidermal growth factor-dependent cell signalling. FEBS J. 2006 Feb;273(4):793-804. PMID:16441665 doi:http://dx.doi.org/10.1111/j.1742-4658.2006.05112.x
- ↑ Steiner E, Holzmann K, Pirker C, Elbling L, Micksche M, Sutterluty H, Berger W. The major vault protein is responsive to and interferes with interferon-gamma-mediated STAT1 signals. J Cell Sci. 2006 Feb 1;119(Pt 3):459-69. Epub 2006 Jan 17. PMID:16418217 doi:http://dx.doi.org/10.1242/jcs.02773
- ↑ Lodwick JE, Shen R, Erramilli S, Xie Y, Roganowicz K, Kossiakoff AA, Zhao M. Structural Insights into the Roles of PARP4 and NAD (+) in the Human Vault Cage. bioRxiv [Preprint]. 2024 Jun 27:2024.06.27.601040. PMID:38979142 doi:10.1101/2024.06.27.601040
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