Investigation of structural and dynamic properties of the Butyrophilin BTN3A1/BTN2A1 cytoplasmic complex by 19F solution NMR DOI Open Access
Khiem Nguyen, Chia‐Hung Christine Hsiao, Yiming Jin

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 13, 2025

Abstract Butyrophilin 3A1 (BTN3A1) is an integral membrane protein capable of detecting phosphoantigens, like ( E )‐4‐hydroxy‐3‐methyl‐but‐2‐enyl diphosphate (HMBPP), through its internal B30.2 domain. Detection phosphoantigens leads to interactions with butyrophilin 2A1 and the subsequent activation γδ‐T cells. Though crystallography functional assays have been crucial for determining vital residues BTN3A1/HMBPP/BTN2A1 complex, mechanism signal transduction still unclear. Here, we utilize 19 F solution NMR observe potential conformational dynamic changes specific upon complex formation. With point mutants BTN3A1, show that W421C, T449C, T506C are influenced by HMBPP BTN2A1 association, while T304C, G323C, C387, C511 not impacted. labeling W421C reduces binding affinity toward BTN3A1/HMBPP, which indicates W421 located at interface. T506 away from phosphoantigen site, so observable chemical shift perturbation suggests there a larger change BTN3A1 domain BTN2A1. The juxtamembrane residues, G323C affected, showing localized within BTN3A1. Using were able detect differential modes synthetic analogs, it possible assess differences in conformations induced different ligands. Taken together, these findings illustrate processes involved detection receptor.

Language: Английский

Investigation of structural and dynamic properties of the Butyrophilin BTN3A1/BTN2A1 cytoplasmic complex by 19F solution NMR DOI Open Access
Khiem Nguyen, Chia‐Hung Christine Hsiao, Yiming Jin

et al.

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(6)

Published: March 13, 2025

Abstract Butyrophilin 3A1 (BTN3A1) is an integral membrane protein capable of detecting phosphoantigens, like ( E )‐4‐hydroxy‐3‐methyl‐but‐2‐enyl diphosphate (HMBPP), through its internal B30.2 domain. Detection phosphoantigens leads to interactions with butyrophilin 2A1 and the subsequent activation γδ‐T cells. Though crystallography functional assays have been crucial for determining vital residues BTN3A1/HMBPP/BTN2A1 complex, mechanism signal transduction still unclear. Here, we utilize 19 F solution NMR observe potential conformational dynamic changes specific upon complex formation. With point mutants BTN3A1, show that W421C, T449C, T506C are influenced by HMBPP BTN2A1 association, while T304C, G323C, C387, C511 not impacted. labeling W421C reduces binding affinity toward BTN3A1/HMBPP, which indicates W421 located at interface. T506 away from phosphoantigen site, so observable chemical shift perturbation suggests there a larger change BTN3A1 domain BTN2A1. The juxtamembrane residues, G323C affected, showing localized within BTN3A1. Using were able detect differential modes synthetic analogs, it possible assess differences in conformations induced different ligands. Taken together, these findings illustrate processes involved detection receptor.

Language: Английский

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