Structure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.

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TitleStructure of natural killer cell receptor KLRG1 bound to E-cadherin reveals basis for MHC-independent missing self recognition.
Publication TypeJournal Article
Year of Publication2009
AuthorsLi, Y, Hofmann, M, Wang, Q, Teng, L, Chlewicki, LK, Pircher, H, Mariuzza, RA
JournalImmunity
Volume31
Issue1
Pagination35-46
Date Published2009 Jul 17
ISSN1097-4180
KeywordsAmino Acid Sequence, Animals, Antigens, CD, Cadherins, Cloning, Molecular, Crystallization, Humans, Integrin alpha Chains, Killer Cells, Natural, Lectins, C-Type, Major Histocompatibility Complex, Mice, Molecular Sequence Data, Protein Conformation, Receptors, Immunologic, Recombinant Proteins, Sequence Alignment, Trans-Activators
Abstract

The cytolytic activity of natural killer (NK) cells is regulated by inhibitory receptors that detect the absence of self molecules on target cells. Structural studies of missing self recognition have focused on NK receptors that bind MHC. However, NK cells also possess inhibitory receptors specific for non-MHC ligands, notably cadherins, which are downregulated in metastatic tumors. We determined the structure of killer cell lectin-like receptor G1 (KLRG1) in complex with E-cadherin. KLRG1 mediates missing self recognition by binding to a highly conserved site on classical cadherins, enabling it to monitor expression of several cadherins (E-, N-, and R-) on target cells. This site overlaps the site responsible for cell-cell adhesion but is distinct from the integrin alpha(E)beta(7) binding site. We propose that E-cadherin may coengage KLRG1 and alpha(E)beta(7) and that KLRG1 overcomes its exceptionally weak affinity for cadherins through multipoint attachment to target cells, resulting in inhibitory signaling.

DOI10.1016/j.immuni.2009.04.019
Alternate JournalImmunity
PubMed ID19604491
PubMed Central IDPMC3030123
Grant ListAI47990 / AI / NIAID NIH HHS / United States
R01 AI047990-09 / AI / NIAID NIH HHS / United States