1 research outputs found
Preferred Orientations of Phosphoinositides in Bilayers and Their Implications in Protein Recognition Mechanisms
Phosphoinositides (PIPs), phosphorylated
derivatives of phosphatidylinositol
(PI), are essential regulatory lipids involved in various cellular
processes, including signal transduction, membrane trafficking, and
cytoskeletal remodeling. To gain insight into the protein-PIPs recognition
process, it is necessary to study the inositol ring orientation (with
respect to the membrane) of PIPs with different phosphorylation states.
In this study, 8 PIPs (3 PIP, 2 PIP<sub>2</sub>, and 3 PIP<sub>3</sub>) with different phosphorylation and protonation sites have been
separately simulated in two mixed bilayers (one with 20% phosphatidylserine
(PS) lipids and another with PS lipids switched to phosphatidylcholine
(PC) lipids), which roughly correspond to yeast membranes. Uniformity
of the bilayer properties including hydrophobic thickness, acyl chain
order parameters, and heavy atom density profiles is observed in both
PS-contained and PC-enriched membranes due to the same hydrophobic
core composition. The relationship between the inositol ring orientation
(tilt and rotation angles) and its solvent-accessible surface area
indicates that the orientation is mainly determined by its solvation
energy. Different PIPs exhibit a clear preference in the inositol
ring rotation angle. Surprisingly, a larger proportion of PIPs inositol
rings stay closer to the surface of PS-contained membranes compared
to PC-enriched ones. Such a difference is rationalized with the formation
of more hydrogen bonds between the PS/PI headgroups and the PIPs inositol
rings in PS-contained membranes. This hydrogen bond network could
be functionally important; thus, the present results can potentially
add important and detailed features into the existing protein-PIPs
recognition mechanism