View source for 7mno


==Crystal structure of the N-terminal domain of NUP358/RanBP2 (residues 1-752) I656V mutant in complex with Fab fragment==
<StructureSection load='7mno' size='340' side='right'caption='[[7mno]], [[Resolution|resolution]] 6.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mno]] is a 6 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=7MNO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MNO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 6.73&#8491;</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=7mno FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mno OCA], [https://pdbe.org/7mno PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mno RCSB], [https://www.ebi.ac.uk/pdbsum/7mno PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mno ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN] Defects in RANBP2 are the cause of encephalopathy acute infection-induced type 3 (IIAE3) [MIM:[https://omim.org/entry/608033 608033]. A rapidly progressive encephalopathy manifesting in susceptibile individuals with seizures and coma. It can occur within days in otherwise healthy children after common viral infections such as influenza and parainfluenza, without evidence of viral infection of the brain or inflammatory cell infiltration. Brain T2-weighted magnetic resonance imaging reveals characteristic symmetric lesions present in the thalami, pons and brainstem. Note=Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).<ref>PMID:19118815</ref> 
== Function ==
[https://www.uniprot.org/uniprot/RBP2_HUMAN RBP2_HUMAN] E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I. Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates. Could also have isomerase or chaperone activity and may bind RNA or DNA. Component of the nuclear export pathway. Specific docking site for the nuclear export factor exportin-1.<ref>PMID:11792325</ref> <ref>PMID:12032081</ref> <ref>PMID:15378033</ref> <ref>PMID:15931224</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
INTRODUCTION The subcellular compartmentalization of eukaryotic cells requires selective transport of folded proteins and protein-nucleic acid complexes. Embedded in nuclear envelope pores, which are generated by the circumscribed fusion of the inner and outer nuclear membranes, nuclear pore complexes (NPCs) are the sole bidirectional gateways for nucleocytoplasmic transport. The ~110-MDa human NPC is an ~1000-protein assembly that comprises multiple copies of ~34 different proteins, collectively termed nucleoporins. The symmetric core of the NPC is composed of an inner ring encircling the central transport channel and outer rings formed by Yâshaped coat nucleoporin complexes (CNCs) anchored atop both sides of the nuclear envelope. The outer rings are decorated with compartmentâspecific asymmetric nuclear basket and cytoplasmic filament nucleoporins, which establish transport directionality and provide docking sites for transport factors and the small guanosine triphosphatase Ran. The cytoplasmic filament nucleoporins also play an essential role in the irreversible remodeling of messenger ribonucleoprotein particles (mRNPs) as they exit the central transport channel. Unsurprisingly, the NPC's cytoplasmic face represents a hotspot for diseaseâassociated mutations and is commonly targeted by viral virulence factors. RATIONALE Previous studies established a near-atomic composite structure of the human NPC's symmetric core by combining (i) biochemical reconstitution to elucidate the interaction network between symmetric nucleoporins, (ii) crystal and single-particle cryo-electron microscopy structure determination of nucleoporins and nucleoporin complexes to reveal their three-dimensional shape and the molecular details of their interactions, (iii) quantitative docking in cryo-electron tomography (cryo-ET) maps of the intact human NPC to uncover nucleoporin stoichiometry and positioning, and (iv) cellâbased assays to validate the physiological relevance of the biochemical and structural findings. In this work, we extended our approach to the cytoplasmic filament nucleoporins to reveal the near-atomic architecture of the cytoplasmic face of the human NPC. RESULTS Using biochemical reconstitution, we elucidated the protein-protein and protein-RNA interaction networks of the human and Chaetomium thermophilum cytoplasmic filament nucleoporins, establishing an evolutionarily conserved heterohexameric cytoplasmic filament nucleoporin complex (CFNC) held together by a central heterotrimeric coiledâcoil hub that tethers two separate mRNPâremodeling complexes. Further biochemical analysis and determination of a series of crystal structures revealed that the metazoanâspecific cytoplasmic filament nucleoporin NUP358 is composed of 16 distinct domains, including an Nâterminal Sâshaped alphaâhelical solenoid followed by a coiledâcoil oligomerization element, numerous Ranâinteracting domains, an E3 ligase domain, and a Câterminal prolylâisomerase domain. Physiologically validated quantitative docking into cryo-ET maps of the intact human NPC revealed that pentameric NUP358 bundles, conjoined by the oligomerization element, are anchored through their Nâterminal domains to the central stalk regions of the CNC, projecting flexibly attached domains as far as ~600 A into the cytoplasm. Using cellâbased assays, we demonstrated that NUP358 is dispensable for the architectural integrity of the assembled interphase NPC and RNA export but is required for efficient translation. After NUP358 assignment, the remaining 4-shaped cryoâET density matched the dimensions of the CFNC coiledâcoil hub, in close proximity to an outer-ring NUP93. Whereas the N-terminal NUP93 assembly sensor motif anchors the properly assembled related coiledâcoil channel nucleoporin heterotrimer to the inner ring, biochemical reconstitution confirmed that the NUP93 assembly sensor is reused in anchoring the CFNC to the cytoplasmic face of the human NPC. By contrast, two C. thermophilum CFNCs are anchored by a divergent mechanism that involves assembly sensors located in unstructured portions of two CNC nucleoporins. Whereas unassigned cryoâET density occupies the NUP358 and CFNC binding sites on the nuclear face, docking of the nuclear basket component ELYS established that the equivalent position on the cytoplasmic face is unoccupied, suggesting that mechanisms other than steric competition promote asymmetric distribution of nucleoporins. CONCLUSION We have substantially advanced the biochemical and structural characterization of the asymmetric nucleoporins' architecture and attachment at the cytoplasmic and nuclear faces of the NPC. Our nearâatomic composite structure of the human NPC's cytoplasmic face provides a biochemical and structural framework for elucidating the molecular basis of mRNP remodeling, viral virulence factor interference with NPC function, and the underlying mechanisms of nucleoporin diseases at the cytoplasmic face of the NPC. [Figure: see text].

Architecture of the cytoplasmic face of the nuclear pore.,Bley CJ, Nie S, Mobbs GW, Petrovic S, Gres AT, Liu X, Mukherjee S, Harvey S, Huber FM, Lin DH, Brown B, Tang AW, Rundlet EJ, Correia AR, Chen S, Regmi SG, Stevens TA, Jette CA, Dasso M, Patke A, Palazzo AF, Kossiakoff AA, Hoelz A Science. 2022 Jun 10;376(6598):eabm9129. doi: 10.1126/science.abm9129. Epub 2022 , Jun 10. PMID:35679405<ref>PMID:35679405</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7mno" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bley CJ]]
[[Category: Brown B]]
[[Category: Chen S]]
[[Category: Correia AR]]
[[Category: Dasso M]]
[[Category: Gres AT]]
[[Category: Harvey S]]
[[Category: Hoelz A]]
[[Category: Huber FM]]
[[Category: Jette CA]]
[[Category: Kossiakoff AA]]
[[Category: Lin DH]]
[[Category: Liu X]]
[[Category: Mobbs GW]]
[[Category: Mukherjee S]]
[[Category: Nie S]]
[[Category: Palazzo AF]]
[[Category: Patke A]]
[[Category: Petrovic S]]
[[Category: Regmi SG]]
[[Category: Rundlet EJ]]
[[Category: Stevens TA]]
[[Category: Tang AW]]