3hw2
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of the SifA-SKIP(PH) complex== | |
| - | + | <StructureSection load='3hw2' size='340' side='right' caption='[[3hw2]], [[Resolution|resolution]] 3.30Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3hw2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Salty Salty]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HW2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3HW2 FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cxb|3cxb]]</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=3hw2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hw2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3hw2 RCSB], [http://www.ebi.ac.uk/pdbsum/3hw2 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[http://www.uniprot.org/uniprot/SIFA_SALTY SIFA_SALTY]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is required for endosomal tubulation and formation of Salmonella-induced filaments (Sifs), which are filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Sif formation is concomitant with intracellular bacterial replication.<ref>PMID:12010459</ref> <ref>PMID:15905402</ref> <ref>PMID:18996344</ref> [[http://www.uniprot.org/uniprot/PKHM2_HUMAN PKHM2_HUMAN]] May play a role in the regulation of conventional kinesin activity. Required for maintenance of the Golgi apparatus organization. May play a role in membrane tubulation.<ref>PMID:15905402</ref> | [[http://www.uniprot.org/uniprot/SIFA_SALTY SIFA_SALTY]] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protein is required for endosomal tubulation and formation of Salmonella-induced filaments (Sifs), which are filamentous structures containing lysosomal membrane glycoproteins within epithelial cells. Sif formation is concomitant with intracellular bacterial replication.<ref>PMID:12010459</ref> <ref>PMID:15905402</ref> <ref>PMID:18996344</ref> [[http://www.uniprot.org/uniprot/PKHM2_HUMAN PKHM2_HUMAN]] May play a role in the regulation of conventional kinesin activity. Required for maintenance of the Golgi apparatus organization. May play a role in membrane tubulation.<ref>PMID:15905402</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/3hw2_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | SifA is a Salmonella effector that is translocated into infected cells by the pathogenicity island 2-encoded type 3 secretion system. SifA is a critical virulence factor. Previous studies demonstrated that, upon translocation, SifA binds the pleckstrin homology motif of the eukaryotic host protein SKIP. In turn, the SifA-SKIP complex regulates the mobilization of the molecular motor kinesin-1 on the bacterial vacuole. SifA exhibits multiple domains containing functional motifs. Here we performed a molecular dissection and a mutational study of SifA to evaluate the relative contribution of the different domains to SifA functions. Biochemical and crystallographic analysis confirmed that the N-terminal domain of SifA is sufficient to interact with the pleckstrin homology domain of SKIP, forming a 1:1 complex with a micromolar dissociation constant. Mutation of the tryptophan residue in the WXXXE motif, which has been proposed to mimic active form of GTPase, deeply affected the stability and the translocation of SifA while mutations of the glutamic residue had no functional impact. A SifA L130D mutant that does not bind SKIP showed a DeltasifA-like phenotype both in infected cells and in the mouse model of infection. We concluded that the WXXXE motif is essential for maintaining the tertiary structure of SifA, the functions of which require the interaction with the eukaryotic protein SKIP. | ||
| - | + | Interaction between the SifA virulence factor and its host target SKIP is essential for Salmonella pathogenesis.,Diacovich L, Dumont A, Lafitte D, Soprano E, Guilhon AA, Bignon C, Gorvel JP, Bourne Y, Meresse S J Biol Chem. 2009 Nov 27;284(48):33151-60. Epub 2009 Sep 28. PMID:19801640<ref>PMID:19801640</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Salty]] | [[Category: Salty]] | ||
| - | [[Category: Bignon, C | + | [[Category: Bignon, C]] |
| - | [[Category: Bourne, Y | + | [[Category: Bourne, Y]] |
| - | [[Category: Diacovich, L | + | [[Category: Diacovich, L]] |
| - | [[Category: Dumont, A | + | [[Category: Dumont, A]] |
| - | [[Category: Gorvel, J P | + | [[Category: Gorvel, J P]] |
| - | [[Category: Guilhon, A A | + | [[Category: Guilhon, A A]] |
| - | [[Category: Lafitte, D | + | [[Category: Lafitte, D]] |
| - | [[Category: Meresse, S | + | [[Category: Meresse, S]] |
| - | [[Category: Soprano, E | + | [[Category: Soprano, E]] |
[[Category: Late effector]] | [[Category: Late effector]] | ||
[[Category: Phosphoprotein]] | [[Category: Phosphoprotein]] | ||
Revision as of 03:08, 25 December 2014
Crystal structure of the SifA-SKIP(PH) complex
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Categories: Human | Salty | Bignon, C | Bourne, Y | Diacovich, L | Dumont, A | Gorvel, J P | Guilhon, A A | Lafitte, D | Meresse, S | Soprano, E | Late effector | Phosphoprotein | Protein complex | Salmonella infection | Sifa | Signaling protein | Virulence
