title: Hydrophobically stabilized open state for the lateral gate of the Sec translocon.
abstract: The Sec translocon is a central component of cellular pathways for protein translocation and membrane integration. Using both atomistic and coarse-grained molecular simulations, we investigate the conformational landscape of the translocon and explore the role of peptide substrates in the regulation of the translocation and integration pathways. Inclusion of a hydrophobic peptide substrate in the translocon stabilizes the opening of the lateral gate for membrane integration, whereas a hydrophilic peptide substrate favors the closed lateral gate conformation. The relative orientation of the plug moiety and a peptide substrate within the translocon channel is similarly dependent on whether the substrate is hydrophobic or hydrophilic in character, and the energetics of the translocon lateral gate opening in the presence of a peptide substrate is governed by the energetics of the peptide interface with the membrane. Implications of these results for the regulation of Sec-mediated pathways for protein translocation vs. membrane integration are discussed.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Miller
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism*; D055592:Biophysical Phenomena; D057927:Hydrophobic and Hydrophilic Interactions; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D046912:Multiprotein Complexes; D055550:Protein Stability; D021381:Protein Transport; D013816:Thermodynamics
chemical_list: D019843:Archaeal Proteins; D026901:Membrane Transport Proteins; D046912:Multiprotein Complexes