View source for 8alk


==Structure of the Legionella phosphocholine hydrolase Lem3 in complex with its substrate Rab1==
<StructureSection load='8alk' size='340' side='right'caption='[[8alk]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8alk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ALK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ALK 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]] 2.15&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=OJU:2-[[[5-(4-azanyl-2-oxidanylidene-pyrimidin-1-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxyethyl-[3-(2-chloranylethanoylamino)propyl]-dimethyl-azanium'>OJU</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=8alk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8alk OCA], [https://pdbe.org/8alk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8alk RCSB], [https://www.ebi.ac.uk/pdbsum/8alk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8alk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LEM3_LEGPH LEM3_LEGPH] Virulence effector that plays a role in hijacking the host vesicular trafficking by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole (LCVs). Acts as a phosphocholine hydrolase by mediating the hydrolysis of phosphocholine to Ser residues of host RAB1 (RAB1A, RAB1B or RAB1C). Dephosphocholination of target proteins restores accessibility to GTPase effector LepB. Can act on both GDP-bound and GTP-bound Rab proteins.<ref>PMID:22158903</ref> <ref>PMID:22307087</ref> <ref>PMID:22411835</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bacterial pathogens often make use of post-translational modifications to manipulate host cells. Legionella pneumophila, the causative agent of Legionnaires disease, secretes the enzyme AnkX that uses cytidine diphosphate-choline to post-translationally modify the human small G-Protein Rab1 with a phosphocholine moiety at Ser76. Later in the infection, the Legionella enzyme Lem3 acts as a dephosphocholinase, hydrolytically removing the phosphocholine. While the molecular mechanism for Rab1 phosphocholination by AnkX has recently been resolved, structural insights into the activity of Lem3 remained elusive. Here, we stabilise the transient Lem3:Rab1b complex by substrate mediated covalent capture. Through crystal structures of Lem3 in the apo form and in complex with Rab1b, we reveal Lem3's catalytic mechanism, showing that it acts on Rab1 by locally unfolding it. Since Lem3 shares high structural similarity with metal-dependent protein phosphatases, our Lem3:Rab1b complex structure also sheds light on how these phosphatases recognise protein substrates.

Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b.,Kaspers MS, Pogenberg V, Pett C, Ernst S, Ecker F, Ochtrop P, Groll M, Hedberg C, Itzen A Nat Commun. 2023 Apr 19;14(1):2245. doi: 10.1038/s41467-023-37621-7. PMID:37076474<ref>PMID:37076474</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8alk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ras-related protein Rab 3D structures|Ras-related protein Rab 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Legionella pneumophila]]
[[Category: Hedberg C]]
[[Category: Itzen A]]
[[Category: Kaspers MS]]
[[Category: Pett C]]
[[Category: Pogenberg V]]