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

Jonathan Back1, Emilio L Malchiodi, Sangwoo Cho

  • 1Ludwig Institute for Cancer Research Ltd., Lausanne Branch and University of Lausanne, 1066 Epalinges, Switzerland.

Immunity
|October 13, 2009
PubMed

Insights

Ly49 natural killer (NK) cell receptors bind MHC class I (MHC-I) differently in trans versus cis. Distinct receptor conformations explain these binding modes and their functional outcomes.

Area of Science:

  • Immunology
  • Structural Biology
  • Cell Biology

Background:

  • Cell-surface receptors mediate intercellular communication by binding ligands.
  • Ly49 receptors on natural killer (NK) cells bind MHC class I (MHC-I) molecules.
  • The structural mechanisms distinguishing trans (inter-cell) and cis (intra-cell) binding remain unclear.

Purpose of the Study:

  • To elucidate the structural basis for Ly49 receptor binding to MHC-I in trans versus cis.
  • To understand how receptor conformation dictates binding mode and function.
  • To identify the role of Ly49 stalk regions in receptor function.

Main Methods:

  • X-ray crystallography to determine Ly49-MHC-I complex structures.
  • Mutagenesis studies to probe the function of stalk segments.
  • Biochemical assays to assess receptor-ligand interactions.

Main Results:

  • Ly49 receptors adopt a backfolded conformation for bivalent trans-binding of MHC-I.
  • An extended conformation enables monovalent cis-binding of MHC-I.
  • Specific stalk segments are dispensable for trans-binding but crucial for inhibitory function.

Conclusions:

  • Distinct Ly49 receptor conformations (backfolded and extended) define the structural basis for cis-trans binding.
  • Receptor conformation dictates binding valency and functional outcomes.
  • Ly49 stalk regions play multifaceted roles in receptor binding and signaling.

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