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Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)

Killer cell Ig-like receptors (KIRs) regulate the function of human natural killer and T cell subsets. A feature of the KIR locus is the clustering of homologous genes encoding for inhibitory and activating KIR. Inhibitory and activating KIR differ for ligand specificities and/or affinities. In part...

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Detalles Bibliográficos
Autores principales: Saulquin, Xavier, Gastinel, Louis N., Vivier, Eric
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193886/
https://www.ncbi.nlm.nih.gov/pubmed/12668644
http://dx.doi.org/10.1084/jem.20021624
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author Saulquin, Xavier
Gastinel, Louis N.
Vivier, Eric
author_facet Saulquin, Xavier
Gastinel, Louis N.
Vivier, Eric
author_sort Saulquin, Xavier
collection PubMed
description Killer cell Ig-like receptors (KIRs) regulate the function of human natural killer and T cell subsets. A feature of the KIR locus is the clustering of homologous genes encoding for inhibitory and activating KIR. Inhibitory and activating KIR differ for ligand specificities and/or affinities. In particular, we show here with KIR tetramers that activating KIR2DS2 does not bind HLA-Cw3 molecules recognized by inhibitory KIR2DL2, despite 99% extracellular amino acid identity. We also report the 2.3-Å structure of KIR2DS2, which reveals subtle displacements of two residues (Tyr(45) and Gln(71)) involved in the interaction of KIR2DL2 with HLA-Cw3. These results show that KIR molecules cannot tolerate any variability in their three-dimensional structure without altering their MHC class I recognition capacities. Therefore, the mode of recognition used by KIR largely differs from the conformational changes that characterize T cell receptor or NKG2D interaction with their respective ligands.
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spelling pubmed-21938862008-04-11 Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j) Saulquin, Xavier Gastinel, Louis N. Vivier, Eric J Exp Med Brief Definitive Report Killer cell Ig-like receptors (KIRs) regulate the function of human natural killer and T cell subsets. A feature of the KIR locus is the clustering of homologous genes encoding for inhibitory and activating KIR. Inhibitory and activating KIR differ for ligand specificities and/or affinities. In particular, we show here with KIR tetramers that activating KIR2DS2 does not bind HLA-Cw3 molecules recognized by inhibitory KIR2DL2, despite 99% extracellular amino acid identity. We also report the 2.3-Å structure of KIR2DS2, which reveals subtle displacements of two residues (Tyr(45) and Gln(71)) involved in the interaction of KIR2DL2 with HLA-Cw3. These results show that KIR molecules cannot tolerate any variability in their three-dimensional structure without altering their MHC class I recognition capacities. Therefore, the mode of recognition used by KIR largely differs from the conformational changes that characterize T cell receptor or NKG2D interaction with their respective ligands. The Rockefeller University Press 2003-04-07 /pmc/articles/PMC2193886/ /pubmed/12668644 http://dx.doi.org/10.1084/jem.20021624 Text en Copyright © 2003, 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 Brief Definitive Report
Saulquin, Xavier
Gastinel, Louis N.
Vivier, Eric
Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
title Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
title_full Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
title_fullStr Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
title_full_unstemmed Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
title_short Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
title_sort crystal structure of the human natural killer cell activating receptor kir2ds2 (cd158j)
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193886/
https://www.ncbi.nlm.nih.gov/pubmed/12668644
http://dx.doi.org/10.1084/jem.20021624
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