Recently, Prof. OUYANG Bo’s lab from Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, reported an atomic resolution CD28-TMH dimer structure in lipid bilayers, providing a mechanistic understanding of CD28 signaling transduction. The study was published in Structure.
CD28 is an essential costimulatory effector that modulates T cell activation and differentiation. The transmembrane helix of CD28 (CD28-TMH) is one of the key components of chimeric antigen receptors, which also plays a crucial role in regulating the immune responses in addition to the membrane insertion and spanning functions. However, limited information is available about how CD28-TMH assembles and mediates the cross-membrane functionality.
In this study, the researchers revealed a CD28-TMH structure using state-of-the-art nuclear magnetic resonance (NMR) technology, in which a GxxxA motif is the key component for the transmembrane dimeric assembly instead of a previously proposed YxxxxT motif. Mutations of the GxxxA motif not only disrupted the transmembrane dimerization in the full-length CD28 proteins when examined by a bimolecular fluorescence complementation (BiFC) assay, but also altered the enhancement activity of CD28. In contrast, mutating the YxxxxT motif does not affect the transmembrane dimerization of full length CD28, but impairs CD28 activity.
"These results imply that the transmembrane domain of CD28 regulates the signaling transduction in a complicated manner," said Prof. OUYANG.