Details
| Original language | English |
|---|---|
| Pages (from-to) | 440-447 |
| Number of pages | 8 |
| Journal | Journal of structural biology |
| Volume | 185 |
| Issue number | 3 |
| Early online date | 19 Dec 2013 |
| Publication status | Published - Mar 2014 |
| Externally published | Yes |
Abstract
Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding. Strain-specific sequence variability in the surface-exposed loops of PorB which are potentially implicated in TLR2 binding, may explain the difference in TLR2-mediated cell activation in vitro by PorB homologs from the commensal Neisseriae lactamica and the pathogen N. meningitidis. Here, we report a comparative structural analysis of PorB from N. meningitidis serogroup B strain 8765 (63% sequence homology with PorB from N. meningitidis serogroup W135) and a mutant in which amino acid substitutions in the extracellular loop 7 lead to significantly reduced TLR2-dependent activity in vitro. We observe that this mutation both alters the loop conformation and causes dramatic changes of electrostatic surface charge, both of which may affect TLR2 recognition and signaling.
Keywords
- Crystal structure, Neisseriae, Outer membrane protein, Toll-like receptor
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Structural Biology
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In: Journal of structural biology, Vol. 185, No. 3, 03.2014, p. 440-447.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Crystallographic analysis of Neisseria meningitidis PorB extracellular loops potentially implicated in TLR2 recognition
AU - Kattner, Christof
AU - Toussi, Deana N.
AU - Zaucha, Jan
AU - Wetzler, Lee M.
AU - Rüppel, Nadine
AU - Zachariae, Ulrich
AU - Massari, Paola
AU - Tanabe, Mikio
PY - 2014/3
Y1 - 2014/3
N2 - Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding. Strain-specific sequence variability in the surface-exposed loops of PorB which are potentially implicated in TLR2 binding, may explain the difference in TLR2-mediated cell activation in vitro by PorB homologs from the commensal Neisseriae lactamica and the pathogen N. meningitidis. Here, we report a comparative structural analysis of PorB from N. meningitidis serogroup B strain 8765 (63% sequence homology with PorB from N. meningitidis serogroup W135) and a mutant in which amino acid substitutions in the extracellular loop 7 lead to significantly reduced TLR2-dependent activity in vitro. We observe that this mutation both alters the loop conformation and causes dramatic changes of electrostatic surface charge, both of which may affect TLR2 recognition and signaling.
AB - Among all Neisseriae species, Neisseria meningitidis and Neisseria gonorrhoeae are the only human pathogens, causative agents of bacterial meningitis and gonorrhoea, respectively. PorB, a pan-Neisseriae trimeric porin that mediates diffusive transport of essential molecules across the bacterial outer membrane, is also known to activate host innate immunity via Toll-like receptor 2 (TLR2)-mediated signaling. The molecular mechanism of PorB binding to TLR2 is not known, but it has been hypothesized that electrostatic interactions contribute to ligand/receptor binding. Strain-specific sequence variability in the surface-exposed loops of PorB which are potentially implicated in TLR2 binding, may explain the difference in TLR2-mediated cell activation in vitro by PorB homologs from the commensal Neisseriae lactamica and the pathogen N. meningitidis. Here, we report a comparative structural analysis of PorB from N. meningitidis serogroup B strain 8765 (63% sequence homology with PorB from N. meningitidis serogroup W135) and a mutant in which amino acid substitutions in the extracellular loop 7 lead to significantly reduced TLR2-dependent activity in vitro. We observe that this mutation both alters the loop conformation and causes dramatic changes of electrostatic surface charge, both of which may affect TLR2 recognition and signaling.
KW - Crystal structure
KW - Neisseriae
KW - Outer membrane protein
KW - Toll-like receptor
UR - http://www.scopus.com/inward/record.url?scp=84894451153&partnerID=8YFLogxK
U2 - 10.1016/j.jsb.2013.12.006
DO - 10.1016/j.jsb.2013.12.006
M3 - Article
C2 - 24361688
AN - SCOPUS:84894451153
VL - 185
SP - 440
EP - 447
JO - Journal of structural biology
JF - Journal of structural biology
SN - 1047-8477
IS - 3
ER -