AI Article Synopsis
- Common γ chain (γc) cytokine receptors, which include IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are activated when their ectodomains bind to interleukins, but direct interactions between the transmembrane domains (TMDs) of γc and interleukin receptors (ILRs) are also essential for activation.
- The γc TMD can recognize TMDs of various ILRs, indicating a level of specificity despite differences in their sequences.
- Research using nuclear magnetic resonance spectroscopy shows that the interactions between γc TMD and ILRs follow a conserved knob-into-hole recognition mechanism, highlighting the importance of TMD interactions for signaling
Article Abstract
Common γ chain (γc) cytokine receptors, including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21 receptors, are activated upon engagement with a common γc receptor (CD132) by concomitant binding of their ectodomains to an interleukin. In this work, we find that direct interactions between the transmembrane domains (TMDs) of both the γc and the interleukin receptors (ILRs) are also required for receptor activation. Moreover, the same γc TMD can specifically recognize multiple ILR TMDs of diverse sequences within the family. Heterodimer structures of γc TMD bound to IL-7 and IL-9 receptor TMDs-determined in a lipid bilayer-like environment by nuclear magnetic resonance spectroscopy-reveal a conserved knob-into-hole mechanism of recognition that mediates receptor sharing within the membrane. Thus, signaling in the γc receptor family requires specific heterotypic interactions of the TMDs.
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| http://dx.doi.org/10.1126/science.add1219 | DOI Listing |
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