Deciphering the Inter-domain Decoupling in the Gram-negative Bacterial Membrane Insertase

Abstract

AbstractYidC is a protein found in membranes that plays an important role in the process of inserting newly generated proteins into lipid membranes. The SecYEG-dependent complex is responsible for inserting proteins into the lipid bilayer, and this process is facilitated by YidC. In addition, YidC acts as a chaperone during the folding processes of proteins. Multiple investigations have conclusively shown that the gram-positive bacterium YidC has SecY-independent insertion mechanisms. Through the use of microsecond level all-atom molecular dynamics simulations, we have carried out the first in-depth investigation of the YidC protein originating from gram-negative bacteria. This research sheds light on the significance of several structural areas related to YidC at an atomic level by utilizing equilibrium molecular dynamics (MD) simulations. In this research, multiple models of YidC inside the lipid bilayer were constructed in order to achieve a deeper understanding of the critical role of the C2 loop and the extra periplasmic domain present in gram-negative YidC. According to the results of our research, the C2 loop is responsible for the overall stabilization of the protein, most notably in the transmembrane region, and it also has an allosteric influence on the periplasmic domain. We have found critical interactions that contribute to the stability of the protein as well as its functional aspect. Finally, our study provides a hypothetical SecY-independent insertion mechanism for gram-negative bacterial YidC.