View source for 9wus


==Cryo-EM Structure of the Periplasmic Domain of AAA Protease FtsH==
<StructureSection load='9wus' size='340' side='right'caption='[[9wus]], [[Resolution|resolution]] 4.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wus]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9WUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WUS 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]] 4.9&#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=9wus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wus OCA], [https://pdbe.org/9wus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wus RCSB], [https://www.ebi.ac.uk/pdbsum/9wus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wus ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FTSH_ECOLI FTSH_ECOLI] Acts as a processive, ATP-dependent zinc metallopeptidase for both cytoplasmic and membrane proteins. Plays a role in the quality control of integral membrane proteins. Degrades a few membrane proteins that have not been assembled into complexes such as SecY, F(0) ATPase subunit a and YccA, and also cytoplasmic proteins sigma-32, LpxC, KdtA and phage lambda cII protein among others. Degrades membrane proteins in a processive manner starting at either the N- or C-terminus; recognition requires a cytoplasmic tail of about 20 residues with no apparent sequence requirements. It presumably dislocates membrane-spanning and periplasmic segments of the protein into the cytoplasm to degrade them, this probably requires ATP. Degrades C-terminal-tagged cytoplasmic proteins which are tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10SA (SsrA) stable RNA.<ref>PMID:7781608</ref> <ref>PMID:7753838</ref> <ref>PMID:10048027</ref> <ref>PMID:18776015</ref>   As FtsH regulates the levels of both LpxC and KdtA it is required for synthesis of both the protein and lipid components of lipopolysaccharide (LPS).<ref>PMID:7781608</ref> <ref>PMID:7753838</ref> <ref>PMID:10048027</ref> <ref>PMID:18776015</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
FtsH, an AAA + metalloprotease that is essential in bacteria and eukaryotic organelles, maintains cellular homeostasis by degrading misfolded and membrane-associated proteins. Here, we report cryo-EM structures of the Escherichia coli FtsH periplasmic domain (FtsH-PD) revealing insights into its intrinsic conformational flexibility. Our analysis resolved two distinct states: a 4.9 A structure exhibiting the conserved alpha + beta fold and a 7.3 A map representing distinct rotated-helix conformation characterized by 20 degrees clockwise rotation of two alpha helices. These findings support a model where conformational changes are present not only in the FtsH cytosolic domain but also in the periplasmic domain. This flexibility potentially facilitates substrate translocation through a combination of mechanisms involving both the FtsH-PD and the HflKC complexed with FtsH, along with lipid-scramblase activity, to assist in membrane protein extraction. This study offers new perspectives on how conformational changes in the periplasmic domain contribute to FtsH substrate degradation mechanisms.

Cryo-EM Structure of the FtsH Periplasmic Domain Reveals Functional Dynamics.,Goc G, Yadav SKN, Orriss G, Borucu U, Berger I, Schaffitzel C, Kabasakal BV ACS Chem Biol. 2026 Apr 17;21(4):844-851. doi: 10.1021/acschembio.5c01025. Epub , 2026 Apr 7. PMID:41944809<ref>PMID:41944809</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wus" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Berger I]]
[[Category: Borucu U]]
[[Category: Goc G]]
[[Category: Kabasakal BV]]
[[Category: Schaffitzel C]]
[[Category: Yadav S]]