The role of prolines and glycine in the transmembrane domain of LAT

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F21%3A00539844" target="_blank" >RIV/61388955:_____/21:00539844 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/21:00554617 RIV/00216208:11310/21:10440413

Výsledek na webu

<a href="https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15713" target="_blank" >https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15713</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.15713" target="_blank" >10.1111/febs.15713</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The role of prolines and glycine in the transmembrane domain of LAT

Popis výsledku v původním jazyce

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.n

Název v anglickém jazyce

The role of prolines and glycine in the transmembrane domain of LAT

Popis výsledku anglicky

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.n

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

FEBS Journal

ISSN

1742-464X

e-ISSN

1742-4658

Svazek periodika

288

Číslo periodika v rámci svazku

13

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

4039-4052

Kód UT WoS článku

000617213100001

EID výsledku v databázi Scopus

2-s2.0-85100974966