Coarse-Grained Modeling of Minute-Timescale Co-Translational Membrane Protein Integration via the Sec-Translocon
Integration into the cell membrane in the correctly folded structure is essential for membrane protein function. Membrane protein integration takes place at the Sec-translocon and typically occurs during translation of the protein sequence. Although extensive structural data is available, study of the dynamics of Sec-facilitated membrane protein integration is difficult due to roles of long-timescale dynamics and ribosomal translation. We present a coarse grain simulation approach that is capable of reaching the experimentally relevant (i.e., minute) timescales, while retaining the level of detail required for reproducing available experimental data. The CG model enables direct simulation of the dynamics of co-translational integration at the Sec-translocon and analysis of the resulting trajectories provides mechanistic explanations for observed experimental data. We will demonstrate use of this CG model to investigate thermodynamic and kinetic factors that govern membrane protein topology, integration efficiency of trans-membrane domains, and hydrophilic loop translocation.
© 2015 Biophysical Society.