8DDC

Intramembrane recognition between transmembrane domains of IL-7R and common gamma chain

Summary for 8DDC

• Entry DOI: 10.2210/pdb8ddc/pdb
• NMR Information: BMRB: 31026
• Descriptor: Cytokine receptor common subunit gamma, Interleukin-7 receptor subunit alpha (2 entities in total)
• Functional Keywords: common gamma-chain cytokine receptor, transmembrane domain, receptor sharing, membrane protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 7316.75

Authors

Cai, T.,Lenoir Capello, R.,Chou, J.J. (deposition date: 2022-06-17, release date: 2023-07-05, Last modification date: 2024-05-15)

Primary citation

Cai, T.,Lenoir Capello, R.,Pi, X.,Wu, H.,Chou, J.J.
Structural basis of gamma chain family receptor sharing at the membrane level.
Science, 381:569-576, 2023

PubMed 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.

PubMed: 37535730
DOI: 10.1126/science.add1219

Experimental method

SOLUTION NMR