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Multimodal Mass Spe...
Multimodal Mass Spectrometry Identifies a Conserved Protective Epitope in S. pyogenes Streptolysin O
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- Tang, Di (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Gueto-Tettay, Carlos (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,epIgG,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Hjortswang, Elisabeth (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Ströbaek, Joel (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,epIgG,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Ekström, Simon (författare)
- Lund University,Lunds universitet,SciLifeLab Site@Lund,Institutionen för laboratoriemedicin,Medicinska fakulteten,Department of Laboratory Medicine,Faculty of Medicine
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- Happonen, Lotta (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,BioMS,Forskargrupper vid Lunds universitet,Strukturell infektionsmedicin,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Structural Infection Medicine (STRIME)
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- Malmström, Lars (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,epIgG,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Malmström, Johan (författare)
- Lund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine Proteomics,Forskargrupper vid Lunds universitet,SEBRA Sepsis and Bacterial Resistance Alliance,epIgG,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,BioMS,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: Analytical Chemistry. - 1520-6882. ; 96:22, s. 9060-9068
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- An important element of antibody-guided vaccine design is the use of neutralizing or opsonic monoclonal antibodies to define protective epitopes in their native three-dimensional conformation. Here, we demonstrate a multimodal mass spectrometry-based strategy for in-depth characterization of antigen–antibody complexes to enable the identification of protective epitopes using the cytolytic exotoxin Streptolysin O (SLO) from Streptococcus pyogenes as a showcase. We first discovered a monoclonal antibody with an undisclosed sequence capable of neutralizing SLO-mediated cytolysis. The amino acid sequence of both the antibody light and the heavy chain was determined using mass-spectrometry-based de novo sequencing, followed by chemical cross-linking mass spectrometry to generate distance constraints between the antibody fragment antigen-binding region and SLO. Subsequent integrative computational modeling revealed a discontinuous epitope located in domain 3 of SLO that was experimentally validated by hydrogen–deuterium exchange mass spectrometry and reverse engineering of the targeted epitope. The results show that the antibody inhibits SLO-mediated cytolysis by binding to a discontinuous epitope in domain 3, likely preventing oligomerization and subsequent secondary structure transitions critical for pore-formation. The epitope is highly conserved across >98% of the characterized S. pyogenes isolates, making it an attractive target for antibody-based therapy and vaccine design against severe streptococcal infections.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
- NATURVETENSKAP -- Kemi -- Analytisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Analytical Chemistry (hsv//eng)
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