Distinct conformations of Ly49 natural killer cell receptors mediate MHC class I recognition in trans and cis.

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TitleDistinct conformations of Ly49 natural killer cell receptors mediate MHC class I recognition in trans and cis.
Publication TypeJournal Article
Year of Publication2009
AuthorsBack, J, Malchiodi, EL, Cho, S, Scarpellino, L, Schneider, P, Kerzic, MC, Mariuzza, RA, Held, W
JournalImmunity
Volume31
Issue4
Pagination598-608
Date Published2009 Oct 16
ISSN1097-4180
KeywordsAnimals, Histocompatibility Antigens Class I, Immunological Synapses, Killer Cells, Natural, Mice, Mice, Inbred C3H, NK Cell Lectin-Like Receptor Subfamily A, Protein Binding, Protein Conformation, Protein Multimerization
Abstract

Certain cell-surface receptors engage ligands expressed on juxtaposed cells and ligands on the same cell. The structural basis for trans versus cis binding is not known. Here, we showed that Ly49 natural killer (NK) cell receptors bound two MHC class I (MHC-I) molecules in trans when the two ligand-binding domains were backfolded onto the long stalk region. In contrast, dissociation of the ligand-binding domains from the stalk and their reorientation relative to the NK cell membrane allowed monovalent binding of MHC-I in cis. The distinct conformations (backfolded and extended) define the structural basis for cis-trans binding by Ly49 receptors and explain the divergent functional consequences of cis versus trans interactions. Further analyses identified specific stalk segments that were not required for MHC-I binding in trans but were essential for inhibitory receptor function. These data identify multiple distinct roles of stalk regions for receptor function.

DOI10.1016/j.immuni.2009.07.007
Alternate JournalImmunity
PubMed ID19818651
PubMed Central IDPMC2770797
Grant ListAI47990 / AI / NIAID NIH HHS / United States
P30 EB009998 / EB / NIBIB NIH HHS / United States
R01 AI047990-09 / AI / NIAID NIH HHS / United States
TW007972 / TW / FIC NIH HHS / United States