7n10

From Proteopedia

Co-crystal structure of Prx with ComR DNA binding domain

Structural highlights

7n10 is a 3 chain structure with sequence from Streptococcus mutans UA159 and Streptococcus pyogenes MGAS315. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.65Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0H2UWN8_STRP3

Publication Abstract from PubMed

Streptococcus pyogenes, or Group A Streptococcus, is a Gram-positive bacterium that can be both a human commensal and a pathogen. Central to this dichotomy are temperate bacteriophages that incorporate into the bacterial genome as prophages. These genetic elements encode both the phage proteins and the toxins harmful to the human host. One such conserved phage protein, paratox (Prx), is always found encoded adjacent to the toxin genes, and this linkage is preserved during all stages of the phage life cycle. Within S. pyogenes, Prx functions to inhibit the quorum-sensing receptor-signal pair ComRS, the master regulator of natural competence, or the ability to uptake endogenous DNA. However, the mechanism by which Prx directly binds and inhibits the receptor ComR is unknown. To understand how Prx inhibits ComR at the molecular level, we pursued an X-ray crystal structure of Prx bound to ComR. The structural data supported by solution X-ray scattering data demonstrate that Prx induces a conformational change in ComR to directly access its DNA-binding domain. Furthermore, electromobility shift assays and competition binding assays reveal that Prx effectively uncouples the interdomain conformational change required for activation of ComR via the signaling molecule XIP. Although to our knowledge the molecular mechanism of quorum-sensing inhibition by Prx is unique, it is analogous to the mechanism employed by the phage protein Aqs1 in Pseudomonas aeruginosa. Together, this demonstrates an example of convergent evolution between Gram-positive and Gram-negative phages to inhibit quorum-sensing and highlights the versatility of small phage proteins.

Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox.,Rutbeek NR, Rezasoltani H, Patel TR, Khajehpour M, Prehna G J Biol Chem. 2021 Sep;297(3):100992. doi: 10.1016/j.jbc.2021.100992. Epub 2021 , Jul 21. PMID:34298018^[1]

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

References

↑ Rutbeek NR, Rezasoltani H, Patel TR, Khajehpour M, Prehna G. Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox. J Biol Chem. 2021 Sep;297(3):100992. PMID:34298018 doi:10.1016/j.jbc.2021.100992