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==Structure of the Legionella effector, AnkB, in complex with human Skp1==
==Structure of the Legionella effector, AnkB, in complex with human Skp1==
<StructureSection load='5k35' size='340' side='right' caption='[[5k35]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
<StructureSection load='5k35' size='340' side='right'caption='[[5k35]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5k35]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K35 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K35 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5k35]] 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=5K35 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K35 FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k34|5k34]]</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#8491;</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=5k35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k35 OCA], [http://pdbe.org/5k35 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k35 RCSB], [http://www.ebi.ac.uk/pdbsum/5k35 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k35 ProSAT]</span></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=5k35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k35 OCA], [https://pdbe.org/5k35 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k35 RCSB], [https://www.ebi.ac.uk/pdbsum/5k35 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k35 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref>
[https://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ankyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K48-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains. Using X-ray crystallography, we determined the 3D structure of AnkB in complex with Skp1, a component of the human SCF ubiquitination ligase. The structure confirms that AnkB contains an N-terminal F box similar to Skp2 and a C-terminal substrate-binding domain similar to eukaryotic ankyrin repeats. We identified crucial amino acids in the substrate-binding domain of AnkB and showed them to be essential for the function of AnkB in L. pneumophila intracellular proliferation. The study reveals how Legionella uses molecular mimicry to manipulate the host ubiquitination pathway and proliferate intracellularly.


Structural Mimicry by a Bacterial F Box Effector Hijacks the Host Ubiquitin-Proteasome System.,Wong K, Perpich JD, Kozlov G, Cygler M, Abu Kwaik Y, Gehring K Structure. 2017 Feb 7;25(2):376-383. doi: 10.1016/j.str.2016.12.015. Epub 2017, Jan 19. PMID:28111017<ref>PMID:28111017</ref>
==See Also==
 
*[[Ankyrin 3D structures|Ankyrin 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5k35" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Structural genomic]]
[[Category: Homo sapiens]]
[[Category: Gehring, K]]
[[Category: Large Structures]]
[[Category: Kozlov, G]]
[[Category: Legionella pneumophila]]
[[Category: Wong, K]]
[[Category: Gehring K]]
[[Category: Ankyrin repeat]]
[[Category: Kozlov G]]
[[Category: Bacterial effector]]
[[Category: Wong K]]
[[Category: Bsgi]]
[[Category: F-box protein]]
[[Category: Host-pathogen interaction]]
[[Category: Protein binding]]

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