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| | ==The structure of the C-terminus of virulence protein IncE from Chlamydia trachomatis bound to Mus musculus SNX5-PX domain== | | ==The structure of the C-terminus of virulence protein IncE from Chlamydia trachomatis bound to Mus musculus SNX5-PX domain== |
| - | <StructureSection load='5tp1' size='340' side='right' caption='[[5tp1]], [[Resolution|resolution]] 2.31Å' scene=''> | + | <StructureSection load='5tp1' size='340' side='right'caption='[[5tp1]], [[Resolution|resolution]] 2.31Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5tp1]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TP1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TP1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5tp1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Chlamydia_trachomatis_D/UW-3/CX Chlamydia trachomatis D/UW-3/CX] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TP1 FirstGlance]. <br> |
| - | </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=5tp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tp1 OCA], [http://pdbe.org/5tp1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tp1 RCSB], [http://www.ebi.ac.uk/pdbsum/5tp1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tp1 ProSAT]</span></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]] 2.31Å</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=5tp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tp1 OCA], [https://pdbe.org/5tp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tp1 RCSB], [https://www.ebi.ac.uk/pdbsum/5tp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tp1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SNX5_MOUSE SNX5_MOUSE]] Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol lipids. Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin. Plays a role in the internalization of EGFR after EGF stimulation. Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C and is retromer-independent. Together with PIP5K1C facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By similarity). Plays a role in macropinocytosis (PubMed:18854019).[UniProtKB:Q9Y5X3]<ref>PMID:18854019</ref> [[http://www.uniprot.org/uniprot/INCE_CHLTR INCE_CHLTR]] Inclusion membrane protein probably involved in early modification events of the chlamydial inclusion. | + | [https://www.uniprot.org/uniprot/SNX5_MOUSE SNX5_MOUSE] Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol lipids. Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin. Plays a role in the internalization of EGFR after EGF stimulation. Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C and is retromer-independent. Together with PIP5K1C facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By similarity). Plays a role in macropinocytosis (PubMed:18854019).[UniProtKB:Q9Y5X3]<ref>PMID:18854019</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5tp1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5tp1" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Sorting nexin 3D structures|Sorting nexin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Czudnochowski, N]] | + | [[Category: Chlamydia trachomatis D/UW-3/CX]] |
| - | [[Category: Rosenberg, O]] | + | [[Category: Large Structures]] |
| - | [[Category: Host-pathogen]] | + | [[Category: Mus musculus]] |
| - | [[Category: Protein transport]] | + | [[Category: Czudnochowski N]] |
| | + | [[Category: Rosenberg O]] |
| Structural highlights
Function
SNX5_MOUSE Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol lipids. Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin. Plays a role in the internalization of EGFR after EGF stimulation. Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C and is retromer-independent. Together with PIP5K1C facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By similarity). Plays a role in macropinocytosis (PubMed:18854019).[UniProtKB:Q9Y5X3][1]
Publication Abstract from PubMed
Chlamydia trachomatis is an obligate intracellular pathogen that resides in a membrane-bound compartment, the inclusion. The bacteria secrete a unique class of proteins, Incs, which insert into the inclusion membrane and modulate the host-bacterium interface. We previously reported that IncE binds specifically to the Sorting Nexin 5 Phox domain (SNX5-PX) and disrupts retromer trafficking. Here, we present the crystal structure of the SNX5-PX:IncE complex, showing IncE bound to a unique and highly conserved hydrophobic groove on SNX5. Mutagenesis of the SNX5-PX:IncE binding surface disrupts a previously unsuspected interaction between SNX5 and the cation-independent mannose-6-phosphate receptor (CI-MPR). Addition of IncE peptide inhibits the interaction of CI-MPR with SNX5. Finally, C. trachomatis infection interferes with the SNX5:CI-MPR interaction, suggesting that IncE and CI-MPR are dependent on the same binding surface on SNX5. Our results provide new insights into retromer assembly and underscore the power of using pathogens to discover disease-related cell biology.
Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction.,Elwell CA, Czudnochowski N, von Dollen J, Johnson JR, Nakagawa R, Mirrashidi K, Krogan NJ, Engel JN, Rosenberg OS Elife. 2017 Mar 2;6. pii: e22709. doi: 10.7554/eLife.22709. PMID:28252385[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lim JP, Wang JT, Kerr MC, Teasdale RD, Gleeson PA. A role for SNX5 in the regulation of macropinocytosis. BMC Cell Biol. 2008 Oct 14;9:58. doi: 10.1186/1471-2121-9-58. PMID:18854019 doi:10.1186/1471-2121-9-58
- ↑ Elwell CA, Czudnochowski N, von Dollen J, Johnson JR, Nakagawa R, Mirrashidi K, Krogan NJ, Engel JN, Rosenberg OS. Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction. Elife. 2017 Mar 2;6. pii: e22709. doi: 10.7554/eLife.22709. PMID:28252385 doi:http://dx.doi.org/10.7554/eLife.22709
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