Molecular Dynamic Simulation of the Transmembrane Portion of the Thermosensor DesK Chimera in DMPC Membranes

DANIEL E. RODRIGUES; A. SERGIO GARAY; LARISA E. CYBULSKI

Sierra de la Ventana, Provincia de Buenos Aires

Congreso; Reunión Anual Sociedad Argentina de Biofísica XLIII; 2014

Sociedad Argentina de Biofísica

p { margin-bottom: 2.12mm; direction: ltr; color: rgb(0, 0, 0); line-height: 115%; widows: 2; orphans: 2; }p.western { font-family: "Calibri","Arial",sans-serif; font-size: 11pt; }p.cjk { font-family: "Arial Unicode MS",sans-serif; font-size: 11pt; }p.ctl { font-size: 11pt; }a:link { color: rgb(0, 0, 255); }a.western:link { }a.ctl:link { } The Bacillus subtilis histidine kinase DesK is an example of thermosensor integral enzyme that promotes the membrane fluidity when temperature drops below ~30°C. A chimera of 31aa of the transmembrane region has been probed to reproduce the thermosensor ability in native and synthetic membranes. We had previously characterized the structural behavior of that chimera by Molecular Dynamics simulations (MD) at 25 ºC (kinase active) and 37ºC (fosfatase active) and found that at low temperature the C-terminal portion between aa 7:27 present an alpha helix secondary structure. From experimental evidences it is known that the following polar residues that links the chimera to the cytoplasmatic portion of the enzyme plays an important role. We performed MD simulation of this extended peptide in DMPC membrane at both relevant temperatures. We found that the transmembrane portion of the peptide breaks in 3 alpha helix sectors at 25°C and results in a coil structure at 37°C. The linker portion of the peptide protrude from the membrane surface at 25°C more that at 37°C. We have proposed a dimeric structure of the chimera based on these results, experimental information and performed MD simulations to characterize its stability and properties at both temperatures.