A salt-bridge motif involved in ligand binding and large scale domain motions of the maltose binding protein

¹ University of Calgary

^* To whom correspondence should be addressed. E-mail: tieleman{at}ucalgary.ca.

Submitted on June 27, 2005
Revised on July 20, 2005
Accepted on 15 August 2005

	Abstract

The uptake of nutrients is essential for the survival of bacterial cells. Many specialized systems have evolved, such as the maltose-dependent ABC transport system that transfers oligosaccharides through the cytoplasmic membrane. The E. coli maltose/maltodextrin-binding protein (MBP) serves as an initial high-affinity binding component in the periplasm that delivers the bound sugar into the cognate ABC transporter MalFGK2. We have investigated the domain motions induced by the binding of the ligand maltotriose into the binding cleft using molecular dynamics simulations. We find that MBP is predominantly in the open state if ligand free and in the closed state when ligand bound. Oligosaccharide binding induces a closure motion (30.0° rotation), while ligand removal leads to domain opening (32.6° rotation) around a well-defined hinge affecting key areas relevant for chemotaxis and transport. Our simulations suggest that a "hook-and-eye" motif is involved in ligand binding. Upon binding, a salt bridge between Glu111 and Lys15 forms that effectively locks the protein-ligand complex in a semi-closed conformation inhibiting any further opening and promoting complete closure. This previously unrecognized feature seems to secure the ligand in the binding site and keeps MBP in the closed conformation and suggests a role in the initial steps of substrate transport.

Key Words: ABC transporter, domain motion, hook-and-eye motif, ligand binding, molecular dynamics simulation, periplasmic binding protein

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