Abstract
Clustering is a basic event for the initiation of immune cell responses, and simulation analyses of clustering of membrane proteins have been performed. It was claimed that a cluster is formed by the self-assembly induced by protein dimerization with a high binding speed (Woolf and Linderman, Biophys. Chem. 104, 217-227, 2003). We examined the cluster formation with Monte Carlo simulation using two algorithms. The first was that simulation processes were divided into two substeps. All proteins were subjected to movement in the first substep, followed by reaction in the second substep. The second algorithm was that proteins were first selected to react and proteins which did not react were subjected to movement. The self-assembly induced by dimerization was simulated only with the second algorithm. In this algorithm, monomers dissociated from dimers do not move because these monomers are not selected for movement, and a large proportion of such monomers are selected to form dimers in the next step. The self-assembly was again simulated with the first algorithm containing the conditions that monomers dissociated from dimers did not move in the next movement substep. This algorithm seems to be far removed from natural conditions. Thus, it is inferred that the self-assembly induced by dimerization is unlikely in situ, and that some interaction between proteins is required for cluster formation. In contrast to algorithms in previous simulations, our results suggest that it is more appropriate that proteins move to the same direction for a while and reflect when the collision occurs.
Highlights
Cellular signal transduction is initiated by the binding of a ligand to its receptor
We found in this study that different algorithms for Monte Carlo simulation gave different results concerning the cluster formation
We examined the cluster formation with Monte Carlo simulation using two algorithms
Summary
Cellular signal transduction is initiated by the binding of a ligand to its receptor. Clustering of transmembrane proteins on the cell surface was proposed in the lipid raft model of the plasma membrane [6]. Foreign antigens are recognized by T cell antigen receptors (TCR) on the cell surface, and the T cells become activated to initiate an immune response [9]. The membrane organization of TCR on the T cell surface has been investigated [10,11,12]. A linker of activated T cells (LAT) was proposed to exist in “protein islands” on the surface of mast cells and T cells [13]. Microscopic techniques have shown separate clusters of TCR and LAT in pre-activated T cells, and these clusters transiently concatenate into microclusters upon antigen recognition [14]. The co-stimulation of TCR with CD28 was reported to require co-localization of TCR and CD28 at the plasma membrane [15]
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