Part:BBa_K4040002

FcRγ Function Unit

Structure and function of the CARγ: Researchers have identified that the common γ subunit of Fc receptors (FcRγ) have the potential ability to enhance the phagocytosis efficiency of the macrophages. We consequently constructed a chimeric antigen receptor containing the critical function domain of the FcRγ, expecting the permitting function of the FcRγ. There are three parts in our CAR, an αS-scFv extracellular domain targeting the spike(S) protein of the SARS-CoV-2, a CD8 hinge and a CD8 transmembrane domain presented in the αCD19 CAR for T cells permitting the signal transduction, a intracellular domain with the same structure of the FcRγ for the enhancement of the phagocytosis efficiency. The mechanism of the CARγ: The function domain of the CARγ mainly lies in the intracellular domain, namely the cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs). The cytosolic Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) in the intracellular domain of the CARγ will be phosphorylated by Src family kinases when the CARγ is stimulated by its ligands S protein. The expression of S protein on the surface of SARS-CoV-2 is actually a strong stimulus of CARγ-macrophages. The activated Immunoreceptor Tyrosine-based Activation Motifs (ITAMs) will expose the SH2 binding domains for the SH2 matching domain. And the SH2 matching domain contains the kinase ZAP70 and the Syk in the T cells and the macrophages respectively. Protein Syk, a phagocytic signaling effector can then active the downstream signaling transduction cascades and initiate the phagocytosis in our CARγ-macrophages eventually.

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal NgoMIV site found at 799
  Illegal NgoMIV site found at 958
  Illegal NgoMIV site found at 1024
  
• 1000
  INCOMPATIBLE WITH RFC[1000]

  Illegal BsaI.rc site found at 679
  Illegal BsaI.rc site found at 1240
  Illegal BsaI.rc site found at 1249
  Illegal SapI.rc site found at 1197