View source for 8vr4


==Structure of Mycobacterium smegmatis 50S ribosomal subunit bound to HflX and erythromycin:50S-HflX-A-Ery==
<StructureSection load='8vr4' size='340' side='right'caption='[[8vr4]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vr4]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VR4 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ERY:ERYTHROMYCIN+A'>ERY</scene>, <scene name='pdbligand=GCP:PHOSPHOMETHYLPHOSPHONIC+ACID+GUANYLATE+ESTER'>GCP</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=8vr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vr4 OCA], [https://pdbe.org/8vr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vr4 RCSB], [https://www.ebi.ac.uk/pdbsum/8vr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vr4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RL30_MYCS2 RL30_MYCS2] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HflX is a highly conserved ribosome-associated GTPase implicated in rescuing stalled ribosomes and mediating antibiotic resistance in several bacteria, including macrolide-lincosamide antibiotic resistance in mycobacteria. Mycobacterial HflXs carry a distinct N-terminal extension (NTE) and a small insertion, as compared to their eubacterial homologs. Here, we present several high-resolution cryo-EM structures of mycobacterial HflX in complex with the 70S ribosome and its 50S subunit, with and without antibiotics. These structures reveal a distinct mechanism for HflX-mediated ribosome splitting and antibiotic resistance in mycobacteria. Our findings indicate that the NTE of mycobacterial HflX induces persistent disordering of multiple 23S rRNA helices, facilitating the dissociation of the 70S ribosome and generating an inactive pool of 50S subunits. During this process, HflX undergoes a large conformational change that stabilizes its NTE. Mycobacterial HflX also acts as an anti-association factor by binding to predissociated 50S subunits. Our structures show that a mycobacteria-specific insertion in HflX reaches far into the peptidyl transferase center (PTC), such that it would overlap with the ribosome-bound macrolide antibiotics. However, in the presence of antibiotics, this insertion retracts, adjusts around, and interacts with the antibiotic molecules. These results suggest that mycobacterial HflX is agnostic to antibiotic presence in the PTC. It mediates antibiotic resistance by splitting antibiotic-stalled 70S ribosomes and inactivating the resulting 50S subunits.

HflX-mediated drug resistance through ribosome splitting and rRNA disordering in mycobacteria.,Majumdar S, Kashyap A, Koripella RK, Sharma MR, Hurst-Hess K, Manjari SR, Banavali NK, Ghosh P, Agrawal RK Proc Natl Acad Sci U S A. 2025 Feb 11;122(6):e2419826122. doi: , 10.1073/pnas.2419826122. Epub 2025 Feb 6. PMID:39913204<ref>PMID:39913204</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8vr4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycolicibacterium smegmatis MC2 155]]
[[Category: Agrawal RK]]
[[Category: Banavali NK]]
[[Category: Koripella RK]]
[[Category: Majumdar S]]
[[Category: Manjari SR]]
[[Category: Sharma MR]]