7L6Z

Crystal Structure of Peptidyl-Prolyl Cis-Trans Isomerasefrom (PpiB) Streptococcus pneumoniae R6

Summary for 7L6Z

• Entry DOI: 10.2210/pdb7l6z/pdb
• Descriptor: Peptidyl-prolyl cis-trans isomerase, CHLORIDE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• Functional Keywords: structural genomics, center for structural genomics of infectious diseases, csgid, peptidyl-prolyl isomerase, isomerase
• Biological source: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
• Total number of polymer chains: 10
• Total formula weight: 241013.51

Authors

Minasov, G.,Shuvalova, L.,Kiryukhina, O.,Dubrovska, I.,Satchell, K.J.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2020-12-24, release date: 2021-12-01, Last modification date: 2026-02-11)

Primary citation

Agbavor, C.,Torres, M.,Inniss, N.L.,Latimer, S.,Minasov, G.,Shuvalova, L.,Wawrzak, Z.,Borek, D.,Otwinowski, Z.,Stogios, P.J.,Savchenko, A.,Anderson, W.F.,Satchell, K.J.F.,Cahoon, L.A.
Structural analysis of extracellular ATP-independent chaperones of streptococcal species and protein substrate interactions.
Msphere, 10:e0107824-e0107824, 2025

PubMed Abstract: During infection, bacterial pathogens rely on secreted virulence factors to manipulate the host cell. However, in gram-positive bacteria, the molecular mechanisms underlying the folding and activity of these virulence factors after membrane translocation are not clear. Here, we solved the protein structures of two secreted parvulin and two secreted cyclophilin-like peptidyl-prolyl isomerase (PPIase) ATP-independent chaperones found in gram-positive streptococcal species. The extracellular parvulin-type PPIase, PrsA in and maintain dimeric crystal structures reminiscent of folding catalysts that consist of two domains, a PPIase and foldase domain. Structural comparison of the two cyclophilin-like extracellular chaperones from and with other cyclophilins demonstrates that this group of cyclophilin-like chaperones has novel structural appendages formed by 9- and 24-residue insertions. Furthermore, we demonstrate that deletion of and genes impairs the secretion of the cholesterol-dependent pore-forming toxin, pneumolysin in . Using protein pull-down and biophysical assays, we demonstrate a direct interaction between PrsA and SlrA with Ply. Then, we developed chaperone-assisted folding assays that show that the PrsA and SlrA extracellular chaperones accelerate pneumolysin folding. In addition, we demonstrate that SlrA and, for the first time, s PpiA exhibit PPIase activity and can bind the immunosuppressive drug, cyclosporine A. Altogether, these findings suggest a mechanistic role for streptococcal PPIase chaperones in the activity and folding of secreted virulence factors such as pneumolysin.

PubMed: 39878509
DOI: 10.1128/msphere.01078-24

Experimental method

X-RAY DIFFRACTION (1.88 Å)