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FRET detection of lymphocyte function–associated antigen-1 conformational extension

Lymphocyte function–associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes...

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Autores principales: Chigaev, Alexandre, Smagley, Yelena, Haynes, Mark K., Ursu, Oleg, Bologa, Cristian G., Halip, Liliana, Oprea, Tudor, Waller, Anna, Carter, Mark B., Zhang, Yinan, Wang, Wei, Buranda, Tione, Sklar, Larry A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279228/
https://www.ncbi.nlm.nih.gov/pubmed/25378583
http://dx.doi.org/10.1091/mbc.E14-06-1050
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author Chigaev, Alexandre
Smagley, Yelena
Haynes, Mark K.
Ursu, Oleg
Bologa, Cristian G.
Halip, Liliana
Oprea, Tudor
Waller, Anna
Carter, Mark B.
Zhang, Yinan
Wang, Wei
Buranda, Tione
Sklar, Larry A.
author_facet Chigaev, Alexandre
Smagley, Yelena
Haynes, Mark K.
Ursu, Oleg
Bologa, Cristian G.
Halip, Liliana
Oprea, Tudor
Waller, Anna
Carter, Mark B.
Zhang, Yinan
Wang, Wei
Buranda, Tione
Sklar, Larry A.
author_sort Chigaev, Alexandre
collection PubMed
description Lymphocyte function–associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1–specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an unexpected result that can be interpreted as a previously unknown LFA-1 conformation.
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spelling pubmed-42792282015-03-16 FRET detection of lymphocyte function–associated antigen-1 conformational extension Chigaev, Alexandre Smagley, Yelena Haynes, Mark K. Ursu, Oleg Bologa, Cristian G. Halip, Liliana Oprea, Tudor Waller, Anna Carter, Mark B. Zhang, Yinan Wang, Wei Buranda, Tione Sklar, Larry A. Mol Biol Cell Articles Lymphocyte function–associated antigen 1 (LFA-1, CD11a/CD18, αLβ2-integrin) and its ligands are essential for adhesion between T-cells and antigen-presenting cells, formation of the immunological synapse, and other immune cell interactions. LFA-1 function is regulated through conformational changes that include the modulation of ligand binding affinity and molecular extension. However, the relationship between molecular conformation and function is unclear. Here fluorescence resonance energy transfer (FRET) with new LFA-1–specific fluorescent probes showed that triggering of the pathway used for T-cell activation induced rapid unquenching of the FRET signal consistent with extension of the molecule. Analysis of the FRET quenching at rest revealed an unexpected result that can be interpreted as a previously unknown LFA-1 conformation. The American Society for Cell Biology 2015-01-01 /pmc/articles/PMC4279228/ /pubmed/25378583 http://dx.doi.org/10.1091/mbc.E14-06-1050 Text en © 2015 Chigaev et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Chigaev, Alexandre
Smagley, Yelena
Haynes, Mark K.
Ursu, Oleg
Bologa, Cristian G.
Halip, Liliana
Oprea, Tudor
Waller, Anna
Carter, Mark B.
Zhang, Yinan
Wang, Wei
Buranda, Tione
Sklar, Larry A.
FRET detection of lymphocyte function–associated antigen-1 conformational extension
title FRET detection of lymphocyte function–associated antigen-1 conformational extension
title_full FRET detection of lymphocyte function–associated antigen-1 conformational extension
title_fullStr FRET detection of lymphocyte function–associated antigen-1 conformational extension
title_full_unstemmed FRET detection of lymphocyte function–associated antigen-1 conformational extension
title_short FRET detection of lymphocyte function–associated antigen-1 conformational extension
title_sort fret detection of lymphocyte function–associated antigen-1 conformational extension
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279228/
https://www.ncbi.nlm.nih.gov/pubmed/25378583
http://dx.doi.org/10.1091/mbc.E14-06-1050
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