5TP1

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

Summary for 5TP1

• Entry DOI: 10.2210/pdb5tp1/pdb
• Descriptor: Sorting nexin-5, Inclusion membrane protein E (3 entities in total)
• Functional Keywords: host-pathogen, protein transport
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 8
• Total formula weight: 86521.20

Authors

Rosenberg, O.,Czudnochowski, N. (deposition date: 2016-10-19, release date: 2017-08-30, Last modification date: 2023-10-04)

Primary citation

Elwell, C.A.,Czudnochowski, N.,von Dollen, J.,Johnson, J.R.,Nakagawa, R.,Mirrashidi, K.,Krogan, N.J.,Engel, J.N.,Rosenberg, O.S.
Chlamydia interfere with an interaction between the mannose-6-phosphate receptor and sorting nexins to counteract host restriction.
Elife, 6:-, 2017

PubMed Abstract: 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, 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.

PubMed: 28252385
DOI: 10.7554/eLife.22709

Experimental method

X-RAY DIFFRACTION (2.31 Å)