Tunnel Formation Inferred from the I-Form Structures of the Proton-Driven Protein Secretion Motor SecDF

Abstract

Summary: Protein secretion mediated by SecYEG translocon and SecA ATPase is enhanced by membrane-embedded SecDF by using proton motive force. A previous structural study of SecDF indicated that it comprises 12 transmembrane helices that can conduct protons and three periplasmic domains, which form at least two characterized transition states, termed the F and I forms. We report the structures of full-length SecDF in I form at 2.6- to 2.8-Å resolution. The structures revealed that SecDF in I form can generate a tunnel that penetrates the transmembrane region and functions as a proton pathway regulated by a conserved Asp residue of the transmembrane region. In one crystal structure, periplasmic cavity interacts with a molecule, potentially polyethylene glycol, which may mimic a substrate peptide. This study provides structural insights into the Sec protein translocation that allows future analyses to develop a more detailed working model for SecDF. : SecDF, a motor protein, uses proton motive force to facilitate bacterial protein translocation mediated by the SecYEG translocon and SecA ATPase. Furukawa et al. describe high-resolution (2.6–2.8 Å) structures of SecDF in I forms, providing insight into a substrate binding site and a proton transport pathway through SecDF. Keywords: protein translocation, Sec proteins, membrane protein, crystal structure, SecYEG, SecDF