title: Electrostatics and Intrinsic Disorder Drive Translocon Binding of the SRP Receptor FtsY.
abstract: Integral membrane proteins in bacteria are co-translationally targeted to the SecYEG translocon for membrane insertion via the signal recognition particle (SRP) pathway. The SRP receptor FtsY and its N-terminal A domain, which is lacking in any structural model of FtsY, were studied using NMR and fluorescence spectroscopy. The A domain is mainly disordered and highly flexible; it binds to lipids via its N terminus and the C-terminal membrane targeting sequence. The central A domain binds to the translocon non-specifically and maintains disorder. Translocon targeting and binding of the A domain is driven by electrostatic interactions. The intrinsically disordered A domain tethers FtsY to the translocon, and because of its flexibility, allows the FtsY NG domain to scan a large area for binding to the NG domain of ribosome-bound SRP, thereby promoting the formation of the quaternary transfer complex at the membrane.
authors.affiliation: Department of NMR-based Structural Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077, Göttingen, Germany. nils-alexander.lakomek@phys.chem.ethz.ch.|ETH Zurich, Department of Chemistry and Applied Biosciences (D-CHAB), Laboratory of Physical Chemistry (LPC), Vladimir-Prelog-Weg 2, 8093, Zurich, Switzerland. nils-alexander.lakomek@phys.chem.ethz.ch.
authors.forename: Nils-Alexander
authors.initials: NA
authors.lastname: Lakomek
authors.affiliation: Max-Planck Institute for Biophysical Chemistry, Department of Physical Biochemistry, Am Fassberg 11, 37077, Göttingen, Germany.
authors.forename: Albena
authors.initials: A
authors.lastname: Draycheva
authors.affiliation: Max-Planck Institute for Biophysical Chemistry, Department of Physical Biochemistry, Am Fassberg 11, 37077, Göttingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bornemann
authors.affiliation: Max-Planck Institute for Biophysical Chemistry, Department of Physical Biochemistry, Am Fassberg 11, 37077, Göttingen, Germany. wolfgang.wintermeyer@mpibpc.mpg.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wintermeyer
keywords: NMR spectroscopy; biophysics; intrinsically disordered proteins; protein-protein interactions; translocon