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The role of prolines and glycine in the transmembrane domain of LAT
Author(s) -
Glatzová Daniela,
Mavila Harsha,
Saija Maria Chiara,
Chum Tomáš,
Cwiklik Lukasz,
Brdička Tomáš,
Cebecauer Marek
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15713
Subject(s) - transmembrane domain , transmembrane protein , palmitoylation , amino acid , chemistry , biophysics , proline , linker , microbiology and biotechnology , biochemistry , biology , cysteine , enzyme , receptor , computer science , operating system
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.