View source for 4kyi


==Crystal structure of the phospholipase VipD from Legionella pneumophila in complex with the human GTPase Rab5==
<StructureSection load='4kyi' size='340' side='right'caption='[[4kyi]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4kyi]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Legionella_pneumophila_subsp._pneumophila_str._Philadelphia_1 Legionella pneumophila subsp. pneumophila str. Philadelphia 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KYI 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]] 3.075&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4kyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kyi OCA], [https://pdbe.org/4kyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kyi RCSB], [https://www.ebi.ac.uk/pdbsum/4kyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kyi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/RAB5C_HUMAN RAB5C_HUMAN] Protein transport. Probably involved in vesicular traffic (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A challenge for microbial pathogens is to assure that their translocated effector proteins target only the correct host cell compartment during infection. The Legionella pneumophila effector vacuolar protein sorting inhibitor protein D (VipD) localizes to early endosomal membranes and alters their lipid and protein composition, thereby protecting the pathogen from endosomal fusion. This process requires the phospholipase A1 (PLA1) activity of VipD that is triggered specifically on VipD binding to the host cell GTPase Rab5, a key regulator of endosomes. Here, we present the crystal structure of VipD in complex with constitutively active Rab5 and reveal the molecular mechanism underlying PLA1 activation. An active site-obstructing loop that originates from the C-terminal domain of VipD is repositioned on Rab5 binding, thereby exposing the catalytic pocket within the N-terminal PLA1 domain. Substitution of amino acid residues located within the VipD-Rab5 interface prevented Rab5 binding and PLA1 activation and caused a failure of VipD mutant proteins to target to Rab5-enriched endosomal structures within cells. Experimental and computational analyses confirmed an extended VipD-binding interface on Rab5, explaining why this L. pneumophila effector can compete with cellular ligands for Rab5 binding. Together, our data explain how the catalytic activity of a microbial effector can be precisely linked to its subcellular localization.

Structural basis for the recruitment and activation of the Legionella phospholipase VipD by the host GTPase Rab5.,Lucas M, Gaspar AH, Pallara C, Rojas AL, Fernandez-Recio J, Machner MP, Hierro A Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):E3514-23. doi:, 10.1073/pnas.1405391111. Epub 2014 Aug 11. PMID:25114243<ref>PMID:25114243</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4kyi" 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 subsp. pneumophila str. Philadelphia 1]]
[[Category: Fernandez-Recio J]]
[[Category: Gaspar AH]]
[[Category: Hierro A]]
[[Category: Lucas M]]
[[Category: Machner MP]]
[[Category: Pallara C]]
[[Category: Rojas AL]]