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CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence

The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we descr...

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Autores principales: Petrie, Emma J., Clements, Craig S., Lin, Jie, Sullivan, Lucy C., Johnson, Darryl, Huyton, Trevor, Heroux, Annie, Hoare, Hilary L., Beddoe, Travis, Reid, Hugh H., Wilce, Matthew C.J., Brooks, Andrew G., Rossjohn, Jamie
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275392/
https://www.ncbi.nlm.nih.gov/pubmed/18332182
http://dx.doi.org/10.1084/jem.20072525
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author Petrie, Emma J.
Clements, Craig S.
Lin, Jie
Sullivan, Lucy C.
Johnson, Darryl
Huyton, Trevor
Heroux, Annie
Hoare, Hilary L.
Beddoe, Travis
Reid, Hugh H.
Wilce, Matthew C.J.
Brooks, Andrew G.
Rossjohn, Jamie
author_facet Petrie, Emma J.
Clements, Craig S.
Lin, Jie
Sullivan, Lucy C.
Johnson, Darryl
Huyton, Trevor
Heroux, Annie
Hoare, Hilary L.
Beddoe, Travis
Reid, Hugh H.
Wilce, Matthew C.J.
Brooks, Andrew G.
Rossjohn, Jamie
author_sort Petrie, Emma J.
collection PubMed
description The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a “lock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors.
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spelling pubmed-22753922008-09-17 CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence Petrie, Emma J. Clements, Craig S. Lin, Jie Sullivan, Lucy C. Johnson, Darryl Huyton, Trevor Heroux, Annie Hoare, Hilary L. Beddoe, Travis Reid, Hugh H. Wilce, Matthew C.J. Brooks, Andrew G. Rossjohn, Jamie J Exp Med Articles The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2 natural killer (NK) receptor family is a central innate mechanism by which NK cells monitor the expression of other HLA molecules, yet the structural basis of this highly specific interaction is unclear. Here, we describe the crystal structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E, whereas the NKG2A subunit was more peripheral to the interface. Moreover, the invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor surface and chemical complementarity. This unusual binding mode was consistent with mutagenesis data at the CD94-NKG2A–HLA-E interface. There were few conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a “lock and key” interaction is typical of innate receptor–ligand interactions. Nevertheless, the structure also provided insight into how this interaction can be modulated by subtle changes in the peptide ligand or by the pairing of CD94 with other members of the NKG2 family. Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors. The Rockefeller University Press 2008-03-17 /pmc/articles/PMC2275392/ /pubmed/18332182 http://dx.doi.org/10.1084/jem.20072525 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Petrie, Emma J.
Clements, Craig S.
Lin, Jie
Sullivan, Lucy C.
Johnson, Darryl
Huyton, Trevor
Heroux, Annie
Hoare, Hilary L.
Beddoe, Travis
Reid, Hugh H.
Wilce, Matthew C.J.
Brooks, Andrew G.
Rossjohn, Jamie
CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
title CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
title_full CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
title_fullStr CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
title_full_unstemmed CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
title_short CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence
title_sort cd94-nkg2a recognition of human leukocyte antigen (hla)-e bound to an hla class i leader sequence
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275392/
https://www.ncbi.nlm.nih.gov/pubmed/18332182
http://dx.doi.org/10.1084/jem.20072525
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