2020/02/20
Keio University
A research group led by Assistant Professor Eiji Yamamoto of the Faculty of Science and Technology at Keio University and Professor Mark S. P. Sansom of the University of Oxford has elucidated a new binding mode between membrane-bound proteins and biological membranes at the molecular level.
In the cell membrane that covers a cell, various types of proteins and lipid molecules are heterogeneously distributed. Signals for maintaining cellular functions are transmitted when specific proteins and lipids interact with each other on the membrane. Many peripheral membrane proteins involved in intracellular signal transduction have a structure called a pleckstrin homology (PH) domain for binding to the membrane. By binding to lipid molecules called phosphatidylinositol phosphates (PIPs) contained in the membrane, the PH domain allows the protein to stay on the membrane surface. Previous studies have reported that multiple PIPs bind to the PH domain in biological membranes, but it has been unclear how this clustering of PIPs affects the interaction between the PH domain and the biological membrane.
This research group conducted molecular-scale simulations and found that the PH domain has multiple PIP binding sites (ranging from high-affinity to low-affinity sites) and that the binding state of the PH domain on the membrane surface and its affinity for the membrane change depending on the PIP concentration around the PH domain. This suggests at the molecular level that PIP clusters formed within the biological membrane can regulate protein function on the membrane.
The results of this research were published in the American scientific journal "Science Advances" on February 19, 2020 (local time).
Please see below for the full press release.