Number of the records: 1
The role of prolines and glycine in the transmembrane domain of LAT
- 1.0539844 - ÚFCH JH 2022 RIV US eng J - Journal Article
Glatzová, Daniela - Mavila, Harsha - Saija, Maria Chiara - Chum, Tomáš - Cwiklik, Lukasz - Brdička, T. - Cebecauer, Marek
The role of prolines and glycine in the transmembrane domain of LAT.
FEBS Journal. Roč. 288, č. 13 (2021), s. 4039-4052. ISSN 1742-464X. E-ISSN 1742-4658
R&D Projects: GA ČR(CZ) GX19-26854X
Institutional support: RVO:61388955
Keywords : LAT * transmembrane * cells
OECD category: Biochemistry and molecular biology
Impact factor: 5.622, year: 2021
Method of publishing: Open access
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15713
Linker for activation in T cells (LAT) is a critical regulator of T‐cell development and function. It organises signalling events at the plasma membrane. However, the mechanism, which controls LAT localisation at the plasma membrane, is not fully understood. Here, we studied the impact of helix‐breaking amino acids, two prolines and one glycine, in the transmembrane segment on localisation and function of LAT. Using in silico analysis, confocal and super‐resolution imaging and flow cytometry, we demonstrate that central proline residue destabilises transmembrane helix by inducing a kink. The helical structure and dynamics are further regulated by glycine and another proline residue in the luminal part of LAT transmembrane domain. Replacement of these residues with aliphatic amino acids reduces LAT dependence on palmitoylation for sorting to the plasma membrane. However, surface expression of these mutants is not sufficient to recover function of nonpalmitoylated LAT in stimulated T cells. These data indicate that geometry and dynamics of LAT transmembrane segment regulate its localisation and function in immune cells.
Permanent Link: http://hdl.handle.net/11104/0317544
File Download Size Commentary Version Access 0539844.pdf 3 2.9 MB Publisher’s postprint require 0539844preprint.pdf 0 2.9 MB Author´s preprint open-access
Number of the records: 1