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 journalArticle

11 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

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NK Cell Lectin-Like Receptors
Cadherins
T-cells
Natural Killer T-Cells
Natural Killer Cells
Assays
Molecular recognition
Intercellular Junctions
Surface Plasmon Resonance
Cell Surface Receptors
Surface plasmon resonance

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nakamura, S., Kuroki, K., Ohki, I., Sasaki, K., Kajikawa, M., Maruyama, T., ... Maenaka, K. (2009). Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1). Journal of Biological Chemistry, 284(40), 27327-27335. https://doi.org/10.1074/jbc.M109.038802

Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1). / Nakamura, Seiko; Kuroki, Kimiko; Ohki, Izuru; Sasaki, Kaori; Kajikawa, Mizuho; Maruyama, Takuma; Ito, Masayuki; Kameda, Yosuke; Ikura, Mitsuhiko; Yamamoto, Kazuo; Matsumoto, Naoki; Maenaka, Katsumi.

In: Journal of Biological Chemistry, Vol. 284, No. 40, 02.10.2009, p. 27327-27335.

Research output: Contribution to journalArticle

Nakamura, S, Kuroki, K, Ohki, I, Sasaki, K, Kajikawa, M, Maruyama, T, Ito, M, Kameda, Y, Ikura, M, Yamamoto, K, Matsumoto, N & Maenaka, K 2009, 'Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1)', Journal of Biological Chemistry, vol. 284, no. 40, pp. 27327-27335. https://doi.org/10.1074/jbc.M109.038802
Nakamura, Seiko ; Kuroki, Kimiko ; Ohki, Izuru ; Sasaki, Kaori ; Kajikawa, Mizuho ; Maruyama, Takuma ; Ito, Masayuki ; Kameda, Yosuke ; Ikura, Mitsuhiko ; Yamamoto, Kazuo ; Matsumoto, Naoki ; Maenaka, Katsumi. / Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1). In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 40. pp. 27327-27335.
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