Structure of CT584 fromChlamydia trachomatisrefined to 3.05 Å resolution

Abstract

Chlamydia trachomatis is a major cause of various diseases, including blinding trachoma and pelvic inflammatory disease, and is the leading reported sexually transmitted bacterial infection worldwide. All pathogenic Chlamydiae spp. utilize a supramolecular syringe, or type III secretion system (T3SS), to inject proteins into their obligate host in order to propagate infection. Here, the structure of CT584, a T3SS-associated protein, that has been refined to a resolution of 3.05 Å is reported. The CT584 structure is a hexamer comprised of a trimer of dimers. The structure shares a high degree of similarity to the recently reported structure of an orthologous protein, Cpn0803, from Chlamydia pneumoniae, which highlights the highly conserved nature of this protein across these chlamydial species, despite different tissue tropism and disease pathology.

Towards a molecular understanding of endosomal trafficking by Retromer and Retriever

“…A possible clue comes from their intriguing structural similarity to two proteins from the bacterial pathogens Chlamydia trachomatis and C. pneumoniae . CT584 and CPN0803 are proteins of unknown function, but they have N and C‐terminal domains that are structurally similar to the HN and COMM domains, respectively . Both proteins form constitutive dimers via their COMM‐like domain, and then assemble into hexamers containing three copies of this core dimer via extensive interfaces that involve both HN‐like and COMM‐like domains.…”

A working model for the type III secretion mechanism in Chlamydia

“…In support of this notion, CT584 is present in EBs [56], and like the corresponding C. pneumoniae protein Cpn0803 [66], interacts with CdsF [61]. CT584 [7] and Cpn0803 [66] can form hexamers, but solved structures do not resemble those of either class-1 or -2 tip proteins typical of either Salmonella SipD or Yersinia LcrV, respectively [31]. In addition, CT584 has recently been implicated as a potential chaperone [53].…”

Structural insights into the architecture and membrane interactions of the conserved COMMD proteins

“…The C-terminal domain forms a homodimer similar to the Commd9 COMM domain, but possesses two additional C-terminal α-helices. C. trachomatis protein CT584 has an identical structure (PDB ID 4MLK) ( Barta et al, 2013 ). ( C ) Side by side view of Commd9 HN domain, and the N-terminal domain of Cpn0803 (residues 8–98) showing the similarity in the overall secondary structure topology.…”

“…Intriguingly, the clearest structural matches to Commd9 are two closely related proteins from the bacterial species Chlamydia trachomatis (CT584) and Chlamydia pneumoniae (Cpn0803) ( Barta et al, 2013 ; Stone et al, 2012 ) (DALI Z-scores > 7.5). CT584 and Cpn0803 are orthologous proteins found only in chlamydia.…”

“…Several chlamydial proteins are believed to have evolved through horizontal gene transfer from eukaryotic hosts, such as SWIB domain-containing proteins and Swi/Snf2 helicases ( Bastidas and Valdivia, 2016 ; Stephens et al, 1998 ), and it is possible that the CT584/Cpn0803 genes have been acquired in a similar fashion. Both CT584 and Cpn0803 form hexameric structures composed of a trimer of dimers, with the N-terminal domains providing the primary interface for trimer formation ( Barta et al, 2013 ; Stone et al, 2012 ) ( Figure 4—figure supplement 4E ). While full-length recombinant Commd1, Commd7 and Commd9 proteins analysed here form homodimers, it is tempting to speculate that the N-terminal domains of COMMD proteins will contribute to formation of higher-order heteromeric assemblies that are present in the 600 kDa CCC complexes isolated from cultured cells ( Wan et al, 2015 ), the stoichiometries and structures of which remain to be determined.…”