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Structure of CD84 provides insight into SLAM family function

Qingrong Yan1, Vladimir N Malashkevich, Alexander Fedorov

  • 1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Proceedings of the National Academy of Sciences of the United States of America
|June 15, 2007
PubMed

Insights

Signaling Lymphocyte Activation Molecule (SLAM) family receptors, like CD84, self-associate with varying affinities. Structural analysis reveals conserved dimerization, suggesting a role in immune cell interactions within the immunological synapse.

Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Interactions

Background:

  • The Signaling Lymphocyte Activation Molecule (SLAM) family comprises receptors modulating adaptive and innate immunity.
  • SLAM receptors share a common ectodomain structure with variable domains responsible for ligand recognition.
  • CD84, a homophilic SLAM member, enhances IFN-gamma secretion in T cells.

Purpose of the Study:

  • To investigate the self-association properties and structural basis of CD84 homophilic interactions.
  • To compare CD84 dimerization with other SLAM family members.
  • To understand the implications of SLAM family receptor structure and affinity on immune cell function.

Main Methods:

  • Biochemical studies to determine CD84 self-association affinity (K(d)).
  • X-ray crystallography to determine the 2.0 Å crystal structure of the human CD84 immunoglobulin variable domain.
  • Comparative structural analysis with other SLAM family members, such as NTB-A.

Main Results:

  • CD84 exhibits strong self-association with a K(d) in the submicromolar range.
  • The crystal structure reveals an orthogonal homophilic dimer of CD84, similar to NTB-A.
  • Structural and chemical differences at homophilic interfaces prevent undesired heterodimer formation among SLAM family receptors.
  • All two-domain SLAM family homophilic dimers share a kinked organization, approximately 140 Å end-to-end.

Conclusions:

  • SLAM family homophilic affinities vary significantly, potentially influencing distinct signaling behaviors.
  • Conserved structural features of SLAM homophilic dimers facilitate colocalization within the immunological synapse.
  • This colocalization mechanism may enable bridging of T cells and antigen-presenting cells.

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