IAM   02674
INSTITUTO ARGENTINO DE MATEMATICA ALBERTO CALDERON
Unidad Ejecutora - UE
artículos
Título:
A lipid-mediated conformational switch modulates the thermosensing activity of DesK
Autor/es:
MARIA EUGENIA INDA ; MICHEL VANDENBRANDEN; ARIEL FERNANDEZ ; DIEGO DE MENDOZA; JEAN-MARIE RUYSSCHAERT; LARISA ESTEFANIA CYBULSKI
Revista:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Editorial:
NATL ACAD SCIENCES
Referencias:
Lugar: Washington DC, USA; Año: 2014 vol. 111 p. 3579 - 3579
ISSN:
0027-8424
Resumen:
The thermosensor DesK is a multipass transmembrane protein that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves as kinase at low temperature and as phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the amino terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially ?buoy? to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question: ?how is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity?? remains poorly understood. Here we identify a ?linker region? (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave as a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.