4jvs: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of LepB GAP domain from Legionella drancourtii in complex with Rab1-GDP and AlF3== | |||
<StructureSection load='4jvs' size='340' side='right' caption='[[4jvs]], [[Resolution|resolution]] 2.78Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4jvs]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Legionella_drancourtii_llap12 Legionella drancourtii llap12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JVS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JVS FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=AF3:ALUMINUM+FLUORIDE'>AF3</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4jw1|4jw1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LDG_7216 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=658187 Legionella drancourtii LLAP12]), RAB1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jvs RCSB], [http://www.ebi.ac.uk/pdbsum/4jvs PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/RAB1A_HUMAN RAB1A_HUMAN]] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity. | [[http://www.uniprot.org/uniprot/RAB1A_HUMAN RAB1A_HUMAN]] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.Cell Research advance online publication 16 April 2013; doi:10.1038/cr.2013.54. | |||
Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.,Yu Q, Hu L, Yao Q, Zhu Y, Dong N, Wang DC, Shao F Cell Res. 2013 Apr 16. doi: 10.1038/cr.2013.54. PMID:23588383<ref>PMID:23588383</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Legionella drancourtii llap12]] | [[Category: Legionella drancourtii llap12]] | ||
[[Category: Shao, F | [[Category: Shao, F]] | ||
[[Category: Wang, D C | [[Category: Wang, D C]] | ||
[[Category: Yao, Q | [[Category: Yao, Q]] | ||
[[Category: Yu, Q | [[Category: Yu, Q]] | ||
[[Category: Bind and hydrolyze guanosine triphosphate]] | [[Category: Bind and hydrolyze guanosine triphosphate]] | ||
[[Category: Hydrolase activator-protein transport complex]] | [[Category: Hydrolase activator-protein transport complex]] | ||
[[Category: New gap fold]] | [[Category: New gap fold]] | ||
[[Category: Rab1 binding]] | [[Category: Rab1 binding]] | ||
Revision as of 08:19, 25 December 2014
Crystal structure of LepB GAP domain from Legionella drancourtii in complex with Rab1-GDP and AlF3Crystal structure of LepB GAP domain from Legionella drancourtii in complex with Rab1-GDP and AlF3
Structural highlights
Function[RAB1A_HUMAN] Probably required for transit of protein from the ER through Golgi compartment. Binds GTP and GDP and possesses intrinsic GTPase activity. Publication Abstract from PubMedRab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.Cell Research advance online publication 16 April 2013; doi:10.1038/cr.2013.54. Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.,Yu Q, Hu L, Yao Q, Zhu Y, Dong N, Wang DC, Shao F Cell Res. 2013 Apr 16. doi: 10.1038/cr.2013.54. PMID:23588383[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||