Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1)

Seiko Nakamura, Kimiko Kuroki, Izuru Ohki, Kaori Sasaki, Mizuho Kajikawa, Takuma Maruyama, Masayuki Ito, Yosuke Kameda, Mitsuhiko Ikura, Kazuo Yamamoto, Naoki Matsumoto, Katsumi Maenaka

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The killer cell lectin-like receptor G1, KLRG1, is a cell surface receptor expressed on subsets of natural killer (NK) cells and T cells. KLRG1 was recently found to recognize E-cadherin and thus inhibit immune responses by regulating the effector function and the developmental processes of NK and T cells. E-cadherin is expressed on epithelial cells and exhibits Ca2+-dependent homophilic interactions that contribute to cell-cell junctions. However, the mechanism underlying the molecular recognition of KLRG1 by E-cadherin remains unclear. Here, we report structural, binding, and functional analyses of this interaction using multiple methods. Surface plasmon resonance demonstrated that KLRG1 binds the E-cadherin N-terminal domains 1 and 2 with low affinity (Kd ∼7-12 μM), typical of cell-cell recognition receptors. NMR binding studies showed that only a limited N-terminal region of E-cadherin, comprising the homodimer interface, exhibited spectrum perturbation upon KLRG1 complex formation. It was confirmed by binding studies using a series of E-cadherin mutants. Furthermore, killing assays using KLRG1+NK cells and reporter cell assays demonstrated the functional significance of the N-terminal region of E-cadherin. These results suggest that KLRG1 recognizes the N-terminal homodimeric interface of domain 1 of E-cadherin and binds only the monomeric form of E-cadherin to inhibit the immune response. This raises the possibility that KLRG1 detects monomeric E-cadherin at exposed cell surfaces to control the activation threshold of NK and T cells.

Original languageEnglish
Pages (from-to)27327-27335
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number40
DOIs
Publication statusPublished - Oct 2 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1)'. Together they form a unique fingerprint.

Cite this