Plexin-B1 is a single-pass transmembrane protein, belonging to plexin family, which play important roles in axon guidance, angiogenesis, and cancer. Plexin-B1 can receive semaphorin guidance cues, and transfer signals through the lipid membrane. Its Rho GTPase Binding Domain (RBD), which is an intracellular domain, can bind with small Rho GTPases, which can affiliate the signal transduction process. RBD also can self-bind to form a homo-dimer. The dimerization process can compete with its binding with Rho GTPase because of a partial steric hindrance effect. Investigation on the structure and dynamics of RBD monomer and dimer can help understanding the plexin-B1 signal transduction mechanism.Based on molecular dynamics simulation trajectories on both RBD monomer and dimer for a total of 400 ns using NAMD program, four kinds of analysis were performed. It was found that the RBD backbone heavy atoms are more dynamic in two loop regions, with the first loop region being the RBD dimer binding region. After binding, the first loop region loses its dynamic, and becomes stable and more rigid based on dihedral angle correlation calculation results, while the second loop region is as dynamic and flexible as in the monomer form. Transfer entropy calculations [1] show that those two loops can drive the movement of the remaining regions to form a dimer. Since only the first loop region is tightly involved in the binding process, the RBD monomer and dimer have a lot of overlaps in structure, which was proved by the principle component analysis results.Citation:[1]. H. Kamberaj and A. van der Vaart, Biophysical Journal, 97, 1747 (2009).

Structure and dynamics analysis on plexin-B1 Rho GTPase binding domain monomer and dimer

247th National Meeting (2014)

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