Kim Taehoon, Lee Jinhyuk, Im Wonpil
Department of Molecular Biosciences and Center for Bioinformatics, The University of Kansas, Lawrence, Kansas 66047, USA.
Proteins. 2009 Jul;76(1):86-98. doi: 10.1002/prot.22322.
Phospholamban (PLB) is an integral membrane protein of 52 residues that regulates the activity of the sarcoplasmic reticulum calcium pump in cardiac muscle cells through reversible phosphorylation of Ser16. To explore its possible conformations and dynamics in a monomeric state, we have performed comparative molecular dynamics simulations of unphosphorylated and phosphorylated PLB (pPLB) with various orientations in POPC membranes. The simulations indicate that dynamics of the cytoplasmic domain is highly dependent on its interactions with membranes, that is, large conformational changes in the absence of membrane interactions, but very restricted dynamics in their presence. pPLB shows more structural flexibility in its cytoplasmic domain, which is consistent with experimental observations. We have also performed a simulation of a PLB pentameric structure (the so-called bellflower model), recently determined in micelles, to investigate its behaviors in a POPC membrane. The cytoplasmic domain in each monomer shows uncorrelated dynamics and undergoes large conformational changes toward the membrane surface during the simulation, which supports the so-called pinwheel model of the PLB pentamer structure. The hydrophobic nature of the pentameric pore excludes water molecules in the pore region, which illustrates that the pore appears to be an energetic barrier for ion and water translocation.
受磷蛋白（PLB）是一种由52个残基组成的整合膜蛋白，它通过对Ser16进行可逆磷酸化来调节心肌细胞中肌浆网钙泵的活性。为了探究其单体状态下可能的构象和动力学，我们对未磷酸化和磷酸化的PLB（pPLB）在POPC膜中以各种取向进行了比较分子动力学模拟。模拟结果表明，细胞质结构域的动力学高度依赖于其与膜的相互作用，即在没有膜相互作用时会发生大的构象变化，但在有膜相互作用时动力学则受到很大限制。pPLB在其细胞质结构域表现出更大的结构灵活性，这与实验观察结果一致。我们还对最近在胶束中确定的PLB五聚体结构（所谓的风铃草模型）进行了模拟，以研究其在POPC膜中的行为。每个单体中的细胞质结构域表现出不相关的动力学，并且在模拟过程中朝着膜表面发生大的构象变化，这支持了PLB五聚体结构的所谓风车模型。五聚体孔的疏水性排除了孔区域中的水分子，这说明该孔似乎是离子和水转运的能量屏障。
