Segregation of negatively charged phospholipids by the polycationic and farnesylated membrane anchor of Kras.

ABSTRACT: The Kras protein, a member of the Ras family of bio-switches that are frequently mutated in cancer and developmental disorders, becomes functional when anchored to the inner surface of the plasma membrane. It is well known that membrane attachment involves the farnesylated and poylcationic C-terminus of the protein. However, little is known about the structure of the complex and the specific protein-lipid interactions that are responsible for the binding. On the basis of data from extensive (>0.55 μs) molecular dynamics simulations of multiple Kras anchors in bilayers of POPC/POPG lipids (4:1 ratio), we show that, as expected, Kras is tethered to the bilayer surface by specific lysine-POPG salt bridges and by nonspecific farnesyl-phospholipid van der Waals interactions. Unexpectedly, howev

SUBMITTER: Janosi L 

PROVIDER: S-EPMC2998625 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature