9zr7: Difference between revisions
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==Cryo-EM structure of NRAS(Q61K)-BRIL fusion in complex with Fab(BAG2) and Monobody(Mb24)== | |||
<StructureSection load='9zr7' size='340' side='right'caption='[[9zr7]], [[Resolution|resolution]] 3.28Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9zr7]] is a 3 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=9ZR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9ZR7 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]] 3.28Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</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=9zr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9zr7 OCA], [https://pdbe.org/9zr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9zr7 RCSB], [https://www.ebi.ac.uk/pdbsum/9zr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9zr7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/RASN_CAVPO RASN_CAVPO] Signal transducer in the Ras-MAPK signaling pathway that regulates cell proliferation and survival (By similarity). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (By similarity). Recognized by LZTR1 that mediates its ubiquitination by a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex (By similarity).[UniProtKB:P01111][https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Small GTPases play important roles in cellular signaling. Due to their small sizes ( approximately 21 kDa), structural studies of small GTPases have been predominantly performed using x-ray crystallography in which crystal lattice contacts made it challenging to define unperturbed conformations of the key switch regions. Here, we developed a protein-engineering strategy that enables cryo-EM analysis of small soluble proteins and applied to RAS. We fused the C-terminal alpha5 helix of the RAS globular domain to a small protein BRIL by forming a continuous helix, which leaves most RAS surfaces exposed to the solvent and unperturbed, followed by the complex formation with an anti-BRIL Fab. This engineered complex with an increased molecular weight, termed "RAS-lollipop", enabled single-particle cryo-EM of RAS. Using this approach, we determined the cryo-EM structure of NRAS, whose structural studies using crystallography have been the least successful among the RAS isoforms. We revealed the conformations of the switch region and alpha 5 helix that differ from those observed in published crystal structures, and also defined the binding site of an NRAS-specific monobody. We uncovered an unexpected surfactant-like property of this monobody, which reduces orientation biases of particles on cryo-EM grids. Together, this work establishes a platform for visualizing small GTPases and potentially other small proteins with minimal perturbation of their surfaces. | |||
Protein Engineering-Enabled Cryo-EM Investigation of Small GTPases.,Hu Z, Patel UR, Glasser E, Koide A, Koide S J Mol Biol. 2026 Sep 1;438(17):169860. doi: 10.1016/j.jmb.2026.169860. Epub 2026 , May 13. PMID:42134495<ref>PMID:42134495</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9zr7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Hu Z]] | |||
[[Category: Koide S]] | |||