Rigid Rod Model for the Disordered Domains of Ribosomal Stalk Proteins P1P2

Abstract

In eukaryotes, the ribosomal stalk proteins, which are responsible for the recruitment of transcription factors, consist of two P1P2 heterodimers attached onto one copy of P0. Recent NMR structure of full-length P1P2 reveals that their C-terminals are disordered in nature and can extend up to 125A away from the center of the heterodimer. Here, we report a rigid rod model aimed at sampling the structures of the disordered C-terminal tails of P1P2. With sequence-dependent angles and dihedrals, our model is constructed from all-atom (AA) molecular dynamics (MD) simulations of short P1P2 segments. Despite its apparent simplicity, the end-to-end distance and radius of gyration computed with our model are found to be in decent agreement with extensive AA simulations of the entire disordered C-terminals of P1P2. Using our model, we further investigate the experimentally observed correlation between the recruitment efficiency of the ribosome inactivating proteins and the length of P1P2 C-terminal tails. Overall, results of our calculation are in good agreement with experimental measurements based on truncation and insertion studies of P1P2, indicating that our rigid rod model offers an efficient and promising approach in structural and functional study of the disordered domains in the ribosome stalk proteins.