Regulation of the Protein-conducting Channel by a Bound Ribosome

The evolutionarily conserved protein-conducting channel, or translocon, is a transmembrane protein which has the dual functions of allowing nascent proteins to cross the membrane or to insert into the membrane. These functions are carried out in concert with a partner which feeds the nascent protein into the channel. In many cases, this partner is the ribosome. The specific interactions between ribosome and protein-conducting channel have recently come into focus due to the availability of cryo-electron microscopy maps of the ribosome in complex with a channel monomer. We have used a method recently developed in our lab, molecular dynamics flexible fitting (MDFF), to fit atomic-scale structures into these maps. Using our fitted atomic-scale model of the ribosome-channel complex, we have carried out large (2.7 million atoms) equilibrium molecular dynamics simulations in order to investigate how the ribosome induces channel opening, as suggested by recent experiments. We find that the channel-blocking plug becomes more mobile under the ribosome's influence. By performing simulations of protein translocation through the ribosomal protein exit tunnel and into the translocon channel, we have determined what elements of the ribosome interact most strongly with the nascent chain and in what orientation the growing protein inserts into the channel.