Cargando…
The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel
The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bact...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613713/ https://www.ncbi.nlm.nih.gov/pubmed/26181365 http://dx.doi.org/10.1042/BSR20150095 |
_version_ | 1782396318107303936 |
---|---|
author | Dyer, Adam Brown, Gemma Stejskal, Lenka Laity, Peter R. Bingham, Richard J. |
author_facet | Dyer, Adam Brown, Gemma Stejskal, Lenka Laity, Peter R. Bingham, Richard J. |
author_sort | Dyer, Adam |
collection | PubMed |
description | The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane, is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The outer membrane protein A (OmpA) domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work, we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans (EM) rash in Europe. Structural characterization of one these proteins (BAPKO_0422) by SAXS and CD indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25×45 Å (1 Å=0.1 nm). Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal phenylalanine residue commonly found in Proteobacterial OM proteins is replaced by isoleucine/leucine or asparagine. BAPKO_0422 is demonstrated to bind human factor H (fH) and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value. |
format | Online Article Text |
id | pubmed-4613713 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-46137132015-11-02 The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel Dyer, Adam Brown, Gemma Stejskal, Lenka Laity, Peter R. Bingham, Richard J. Biosci Rep Original Papers The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane, is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The outer membrane protein A (OmpA) domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work, we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans (EM) rash in Europe. Structural characterization of one these proteins (BAPKO_0422) by SAXS and CD indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25×45 Å (1 Å=0.1 nm). Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal phenylalanine residue commonly found in Proteobacterial OM proteins is replaced by isoleucine/leucine or asparagine. BAPKO_0422 is demonstrated to bind human factor H (fH) and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value. Portland Press Ltd. 2015-08-18 /pmc/articles/PMC4613713/ /pubmed/26181365 http://dx.doi.org/10.1042/BSR20150095 Text en © 2015 Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article published by Portland Press Limited and distributed under the Creative Commons Attribution Licence 3.0 (http://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Original Papers Dyer, Adam Brown, Gemma Stejskal, Lenka Laity, Peter R. Bingham, Richard J. The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel |
title | The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel |
title_full | The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel |
title_fullStr | The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel |
title_full_unstemmed | The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel |
title_short | The Borrelia afzelii outer membrane protein BAPKO_0422 binds human factor-H and is predicted to form a membrane-spanning β-barrel |
title_sort | borrelia afzelii outer membrane protein bapko_0422 binds human factor-h and is predicted to form a membrane-spanning β-barrel |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613713/ https://www.ncbi.nlm.nih.gov/pubmed/26181365 http://dx.doi.org/10.1042/BSR20150095 |
work_keys_str_mv | AT dyeradam theborreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT browngemma theborreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT stejskallenka theborreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT laitypeterr theborreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT binghamrichardj theborreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT dyeradam borreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT browngemma borreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT stejskallenka borreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT laitypeterr borreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel AT binghamrichardj borreliaafzeliioutermembraneproteinbapko0422bindshumanfactorhandispredictedtoformamembranespanningbbarrel |