7pgt: Difference between revisions

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-'''Unreleased structure'''
-The entry 7pgt is ON HOLD
+==The structure of human neurofibromin isoform 2 in opened conformation.==
+<StructureSection load='7pgt' size='340' side='right'caption='[[7pgt]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PGT 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]] 4.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7pgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pgt OCA], [https://pdbe.org/7pgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pgt RCSB], [https://www.ebi.ac.uk/pdbsum/7pgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pgt ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1)(1,2). As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. We determined the human Nf1 dimer structure at an overall resolution of 3.3 A. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing(3) isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. In a distinctly different, open conformation of one protomer, a large-scale movement of the GRD occurs, which is necessary to access Ras, whereas Sec14-PH reorients to allow interaction with the cellular membrane(4). Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker. The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis.
-Authors:
+The structure of neurofibromin isoform 2 reveals different functional states.,Naschberger A, Baradaran R, Rupp B, Carroni M Nature. 2021 Nov;599(7884):315-319. doi: 10.1038/s41586-021-04024-x. Epub 2021, Oct 27. PMID:34707296<ref>PMID:34707296</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 7pgt" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Neurofibromin|Neurofibromin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Baradaran R]]
+[[Category: Carroni M]]
+[[Category: Naschberger A]]
+[[Category: Rupp B]]