Molecular analyses identifies new domains and structural differences among Streptococcus pneumoniae immune evasion proteins PspC and Hic

Abstract

The PspC and Hic proteins of Streptococcuspneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles, it was assumed for a long time that these pneumococcal surface proteins represent a protein family comprised of eleven subgroups. Recently, however, the evaluation of more proteins revealed a greater diversity of individual proteins. In contrast to previous assumptions a pattern evaluation of six PspC and five Hic variants, each representing one of the previously defined subgroups, revealed distinct structural and likely functionally regions of the proteins, and identified nine new domains and new domain alternates. Several domains are unique to PspC and Hic variants, while other domains are also present in other virulence factors encoded by pneumococci and other bacterial pathogens. This knowledge improved pattern evaluation at the level of full-length proteins, allowed a sequence comparison at the domain level and identified domains with a modular composition. This novel strategy increased understanding of individual proteins variability and modular domain composition, enabled a structural and functional characterization at the domain level and furthermore revealed substantial structural differences between PspC and Hic proteins. Given the exceptional genomic diversity of the multifunctional PspC and Hic proteins a detailed structural and functional evaluation need to be performed at the strain level. Such knowledge will also be useful for molecular strain typing and characterizing PspC and Hic proteins from new clinical S. pneumoniae strains.

Probing the binding nature and stability of highly transmissible mutated variant alpha to omicron of SARS‐CoV‐2 RBD with ACE2 via molecular dynamics simulation

“…Importantly, the knowledge of dynamical binding nature of RBD with ACE2 is also essential to identify the drug targets for the variants which has mutations, this often alter the binding mode of virus and entry mechanism to the host cells. Several reports outline the evidence of conformational change of binding domain that occurs due to the mutations in SARS‐CoV‐2 variants; these previous studies which demonstrate the same with their experimental and computational reports 16–20 . Protein structure of RBD bound with ACE2 have been reported (PDB code: 6M0J) and the binding nature also revealed by J Lan et al which states that the sequence of this protein is highly similar to the SARS‐CoV RBD and has improved binding nature 6 .…”

“…Several reports outline the evidence of conformational change of binding domain that occurs due to the mutations in SARS-CoV-2 variants; these previous studies which demonstrate the same with their experimental and computational reports. [16][17][18][19][20] Protein structure of RBD bound with ACE2 have been reported (PDB code: 6M0J) and the binding nature also revealed by J Lan et al which states that the sequence of this protein is highly similar to the SARS-CoV RBD and has improved binding nature. 6 P Han et al reported an insights into RBD-ACE2 binding for emerging SARS-CoV-2 variants which characterize the binding using cytometry.…”

“…Importantly, the knowledge of dynamical binding nature of RBD with ACE2 is also essential to identify the drug targets for the variants which has mutations, this often alter the binding mode of virus and entry mechanism to the host cells. Several reports outline the evidence of conformational change of binding domain that occurs due to the mutations in SARS-CoV-2 variants [16][17][18][19][20] .…”

The role of pneumococcal extracellular vesicles on the pathophysiology of the kidney disease Hemolytic Uremic Syndrome

“…HUS A strain showed higher H2O2 excretion (~2-fold more than WT) than the other strains assayed. Previously, we showed that HUS A strongly binds lactoferrin (30,31). Thus, the HUS A strain (from now on referred to as the Sp-HUS strain), which was isolated from a 2-year-old patient suffering from HUS, was chosen as the focus for the rest of this study.…”

The choline-binding proteins PspA, PspC, and LytA of Streptococcus pneumoniae and their interaction with human endothelial and red blood cells

“…PspA and PspC share structural similarities: each has modular, unique, and variable N-terminal regions, a proline-rich domain that varies in size and almost identical C-terminal regions ( 27 , 28 ) ( Fig. S1 ).…”