5tp1: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

The ~~entry~~ 5tp1 is ~~ON HOLD~~ ~~until Paper~~ Publication

==The structure of the C-terminus of virulence protein IncE from Chlamydia trachomatis bound to Mus musculus SNX5-PX domain==

== 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>

</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>

</table>

== 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.

== 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.

~~Authors~~:

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<ref>PMID:28252385</ref>

~~Description~~:

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

[[Category: ~~Unreleased Structures~~]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Czudnochowski, N]]

[[Category: Rosenberg, O]]

[[Category: Host-pathogen]]

[[Category: Protein transport]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5tp1 is ON HOLD  until Paper Publication
+==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]] 2.31&Aring;' scene=''>
+== 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>
+</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>
+</table>
+== 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.
+<div style="background-color:#fffaf0;">
+== 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.
-Authors:
+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<ref>PMID:28252385</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5tp1" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Czudnochowski, N]]
+[[Category: Rosenberg, O]]
+[[Category: Host-pathogen]]
+[[Category: Protein transport]]