7VU5

Structure of the transmembrane domain of the CD28 dimer

Summary for 7VU5

• Entry DOI: 10.2210/pdb7vu5/pdb
• Descriptor: T-cell-specific surface glycoprotein CD28 (1 entity in total)
• Functional Keywords: cd28, transmembrane domain, immune system
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 9331.31

Authors

Wu, H.,Cao, R.,Wen, M.,Ouyang, B. (deposition date: 2021-11-01, release date: 2022-03-02, Last modification date: 2024-05-15)

Primary citation

Wu, H.,Cao, R.,Wen, M.,Xue, H.,OuYang, B.
Structural characterization of a dimerization interface in the CD28 transmembrane domain.
Structure, 30:803-812.e5, 2022

PubMed Abstract: CD28 has a crucial role in regulating immune responses by enhancing T cell activation and differentiation. Recent studies have shown that the transmembrane helix (TMH) of CD28 mediates receptor assembly and activity, but a structural characterization of TMH is still lacking. Here, we determined the dimeric helix-helix packing of CD28-TMH using nuclear magnetic resonance (NMR) technology. Unexpectedly, wild-type CD28-TMH alone forms stable tetramers in lipid bicelles instead of dimers. The NMR structure of the CD28-TMH C165F mutant reveals that a GxxxA motif, which is highly conserved in many dimeric assemblies, is located at the dimerization interface. Mutating G160 and A164 can disrupt the transmembrane helix assembly and reduces CD28 enhancement in cells. In contrast, a previously proposed YxxxxT motif does not affect the dimerization of full-length CD28, but it does affect CD28 activity. These results imply that the transmembrane domain of CD28 regulates the signaling transduction in a complicated manner.

PubMed: 35397202
DOI: 10.1016/j.str.2022.03.004

Experimental method

SOLUTION NMR