9mxh

From Proteopedia

(Difference between revisions)

Current revision

Human Vault Cage in complex with NAD+

Structural highlights

9mxh is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.07Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9mxh"

Categories: Homo sapiens | Large Structures | Lodwick JE | Zhao M

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9mxh is ON HOLD  until Paper Publication
+==Human Vault Cage in complex with NAD+==
+<StructureSection load='9mxh' size='340' side='right'caption='[[9mxh]], [[Resolution|resolution]] 3.07&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9mxh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9MXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MXH FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.07&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9mxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9mxh OCA], [https://pdbe.org/9mxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9mxh RCSB], [https://www.ebi.ac.uk/pdbsum/9mxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9mxh ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MVP_HUMAN 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.<ref>PMID:15133037</ref> <ref>PMID:16441665</ref> <ref>PMID:16418217</ref>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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<ref>PMID:38979142</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9mxh" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Lodwick JE]]
+[[Category: Zhao M]]

9mxh

From Proteopedia

Current revision

Human Vault Cage in complex with NAD+

Structural highlights

Function

Publication Abstract from PubMed

References

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