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3hw2

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Revision as of 08:23, 12 December 2018

Crystal structure of the SifA-SKIP(PH) complex

Structural highlights

3hw2 is a 2 chain structure with sequence from Human and Salty. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3cxb
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] [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.^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Brumell JH, Goosney DL, Finlay BB. SifA, a type III secreted effector of Salmonella typhimurium, directs Salmonella-induced filament (Sif) formation along microtubules. Traffic. 2002 Jun;3(6):407-15. PMID:12010459
↑ Boucrot E, Henry T, Borg JP, Gorvel JP, Meresse S. The intracellular fate of Salmonella depends on the recruitment of kinesin. Science. 2005 May 20;308(5725):1174-8. PMID:15905402 doi:308/5725/1174
↑ Ohlson MB, Huang Z, Alto NM, Blanc MP, Dixon JE, Chai J, Miller SI. Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe. 2008 Nov 13;4(5):434-46. PMID:18996344 doi:S1931-3128(08)00291-6
↑ Boucrot E, Henry T, Borg JP, Gorvel JP, Meresse S. The intracellular fate of Salmonella depends on the recruitment of kinesin. Science. 2005 May 20;308(5725):1174-8. PMID:15905402 doi:308/5725/1174
↑ Diacovich L, Dumont A, Lafitte D, Soprano E, Guilhon AA, Bignon C, Gorvel JP, Bourne Y, Meresse S. Interaction between the SifA virulence factor and its host target SKIP is essential for Salmonella pathogenesis. J Biol Chem. 2009 Nov 27;284(48):33151-60. Epub 2009 Sep 28. PMID:19801640 doi:10.1074/jbc.M109.034975

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3hw2"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the SifA-SKIP(PH) complex==
 <StructureSection load='3hw2' size='340' side='right' caption='[[3hw2]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <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>
 </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://pdbe.org/3hw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hw2 RCSB], [http://www.ebi.ac.uk/pdbsum/3hw2 PDBsum]</span></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://pdbe.org/3hw2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3hw2 RCSB], [http://www.ebi.ac.uk/pdbsum/3hw2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3hw2 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 12: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/3hw2_consurf.spt"</scriptWhenChecked>
+    <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>

3hw2

From Proteopedia

Revision as of 08:23, 12 December 2018

Crystal structure of the SifA-SKIP(PH) complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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