TCB Publications - Abstract
Ying Yin, Morten Ø. Jensen, Emad Tajkhorshid, and Klaus Schulten. Sugar binding and protein conformational changes in lactose permease. Biophysical Journal, 91:3972-3985, 2006. (PMC: 1635680)
co-transport have been suggested. Yet, the transport mechanism, especially the coupling
of protonation states of certain residues and protein conformational
changes involved in the transport, is not understood. Here we report
MD simulations of membrane embedded LacY in different protonation
states, both in the presence and in the absence of lactose. The
results analyzed in terms of pore diameter, salt bridge formation
and substrate motion, strongly implicate Glu269 as one of the main
proton translocation sites, whose protonation state controls several
key steps of the transport process. A critical ion pair (Glu269 and
Arg144) was found to keep the cytoplasmic entrance open, however, via a different mechanism from the currently accepted model. After protonation of Glu269, the salt bridge between Glu269 and Arg144
was found to break, and Arg144 to move away from Glu269 establishing a new salt bridge with Glu126; furthermore, neutralization of Glu269 and the displacement of Arg144 and consequently of water molecules from the interdomain region was seen to initiate the
closing of the cytoplasmic half channel (2.6 - 4.0 Å reduction
in diameter in the cytoplasmic constriction region in 10 ns) by
allowing hydrophobic surfaces of the N- and C-domains to fuse.
Charged Glu269 was found to strongly bind the lactose permeant, indicating that proton transfer from water or another residue to Glu269 is a prerequisite for unbinding of lactose from the binding pocket.
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