Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2

Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously repo...

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Main Authors: Abouseada, Noha M., Assafi, Mahde Saleh A., Mahdavi, Jafar, Oldfield, Neil J., Wheldon, Lee M., Wooldridge, Karl G., Ala'Aldeen, Dlawer A.A.
Format: Article
Published: Public Library of Science 2012
Online Access:https://eprints.nottingham.ac.uk/2548/
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author Abouseada, Noha M.
Assafi, Mahde Saleh A.
Mahdavi, Jafar
Oldfield, Neil J.
Wheldon, Lee M.
Wooldridge, Karl G.
Ala'Aldeen, Dlawer A.A.
author_facet Abouseada, Noha M.
Assafi, Mahde Saleh A.
Mahdavi, Jafar
Oldfield, Neil J.
Wheldon, Lee M.
Wooldridge, Karl G.
Ala'Aldeen, Dlawer A.A.
author_sort Abouseada, Noha M.
building Nottingham Research Data Repository
collection Online Access
description Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously reported that a surface-exposed loop of the R2 domain of CbpA mediates LamR-binding. Here we have identified the LamR-binding regions of PorA and OmpP2. Using truncated recombinant proteins we show that binding is dependent on amino acids 171–240 and 91–99 of PorA and OmpP2, respectively, which are predicted to localize to the fourth and second surface-exposed loops, respectively, of these proteins. Synthetic peptides corresponding to the loops bound LamR and could block LamR-binding to bacterial ligands in a dose dependant manner. Meningococci expressing PorA lacking the apex of loop 4 and H. influenzae expressing OmpP2 lacking the apex of loop 2 showed significantly reduced LamR binding. Since both loops are hyper-variable, our data may suggest a molecular basis for the range of LamR-binding capabilities previously reported among different meningococcal and H. influenzae strains.
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spelling nottingham-25482020-05-04T16:33:58Z https://eprints.nottingham.ac.uk/2548/ Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2 Abouseada, Noha M. Assafi, Mahde Saleh A. Mahdavi, Jafar Oldfield, Neil J. Wheldon, Lee M. Wooldridge, Karl G. Ala'Aldeen, Dlawer A.A. Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via the surface protein adhesins: meningococcal PilQ and PorA, H. influenzae OmpP2 and pneumococcal CbpA. We have previously reported that a surface-exposed loop of the R2 domain of CbpA mediates LamR-binding. Here we have identified the LamR-binding regions of PorA and OmpP2. Using truncated recombinant proteins we show that binding is dependent on amino acids 171–240 and 91–99 of PorA and OmpP2, respectively, which are predicted to localize to the fourth and second surface-exposed loops, respectively, of these proteins. Synthetic peptides corresponding to the loops bound LamR and could block LamR-binding to bacterial ligands in a dose dependant manner. Meningococci expressing PorA lacking the apex of loop 4 and H. influenzae expressing OmpP2 lacking the apex of loop 2 showed significantly reduced LamR binding. Since both loops are hyper-variable, our data may suggest a molecular basis for the range of LamR-binding capabilities previously reported among different meningococcal and H. influenzae strains. Public Library of Science 2012-09-25 Article PeerReviewed Abouseada, Noha M., Assafi, Mahde Saleh A., Mahdavi, Jafar, Oldfield, Neil J., Wheldon, Lee M., Wooldridge, Karl G. and Ala'Aldeen, Dlawer A.A. (2012) Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2. PLoS ONE, 7 (9). 10/1-10/10. ISSN 1932-6203 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046233 doi:10.1371/journal.pone.0046233 doi:10.1371/journal.pone.0046233
spellingShingle Abouseada, Noha M.
Assafi, Mahde Saleh A.
Mahdavi, Jafar
Oldfield, Neil J.
Wheldon, Lee M.
Wooldridge, Karl G.
Ala'Aldeen, Dlawer A.A.
Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2
title Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2
title_full Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2
title_fullStr Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2
title_full_unstemmed Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2
title_short Mapping the laminin receptor binding domains of Neisseria meningitidis PorA and Haemophilus influenzae OmpP2
title_sort mapping the laminin receptor binding domains of neisseria meningitidis pora and haemophilus influenzae ompp2
url https://eprints.nottingham.ac.uk/2548/
https://eprints.nottingham.ac.uk/2548/
https://eprints.nottingham.ac.uk/2548/