The adaptability of the ion-binding site by the Ag(I)/Cu(I) periplasmic chaperone SilF
Ryan M Lithgo1, Marko Hanževački2, Gemma Harris3
1School of Biosciences, Sutton Bonington Campus, University of Nottingham, Leicestershire, United Kingdom; Membrane Protein Laboratory, Diamond Light Source, Rutherford Appleton Laboratory, Didcot, Oxfordshire, United Kingdom; Diamond Light Source, Diamond House, Rutherford Appleton Laboratories, Didcot, Oxfordshire, United Kingdom; Research Complex at Harwell, Rutherford Appleton Laboratory, Didcot, Oxfordshire, United Kingdom.
Abstract:
The periplasmic chaperone SilF has been identified as part of an Ag(I) detoxification system in Gram-negative bacteria. Sil proteins also bind Cu(I) but with reported weaker affinity, therefore leading to the designation of a specific detoxification system for Ag(I). Using isothermal titration calorimetry, we show that binding of both ions is not only tighter than previously thought but of very similar affinities. We investigated the structural origins of ion binding using molecular dynamics and QM/MM simulations underpinned by structural and biophysical experiments. The results of this analysis showed that the binding site adapts to accommodate either ion, with key interactions with the solvent in the case of Cu(I). The implications of this are that Gram-negative bacteria do not appear to have evolved a specific Ag(I) efflux system but take advantage of the existing Cu(I) detoxification system. Therefore, there are consequences for how we define a particular metal resistance mechanism and understand its evolution in the environment.
More Related Videos
10:24Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
Published on: June 7, 2018
11:38Quantifying the Binding Interactions Between CuII and Peptide Residues in the Presence and Absence of Chromophores
Published on: April 5, 2022
Related Concept Videos
Molecular Chaperones and Protein Folding
The...
Formation of Complex Ions
Ligand Binding and Linkage
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Bacterial Protein Maturation
