Cardiolipin Selectively Binds to the Interface of VsSemiSWEET and Regulates Its Dimerization.

Abstract

Lipid-regulated oligomerization of membrane proteins plays a critical role in many cell-transduction pathways. However, molecular details of such processes are often hard to define experimentally. Here we reveal the key role of interfacial cardiolipin in regulating the functional dimerization of VsSemiSWEET (one of the smallest transporters) using molecular dynamics simulations. Four binding sites for cardiolipins are identified by calculating the spatiotemporal density distribution of cardiolipins and the free energy surface. Two types of dimerization modes (i.e., arm-to-body and body-to-body) are observed in the assembly process of VsSemiSWEET protomers. Binding of enough cardiolipin molecules at the dimer interface on the cytoplasmic side is found to be crucial in adjusting the monomer-dimer equilibrium and regulating the formation of functional dimers with proper conformation. Our results provide useful information on the relationship between lipid binding and functional dimerization of VsSemiSWEET and are helpful to understand the molecular mechanism of biological function of sugar transporters.