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Structural studies on lactose permease

Reference	BB/C515163/1
Principal Investigator / Supervisor	Professor So Iwata
Co-Investigators / Co-Supervisors
Institution	Imperial College London
Department	Biological Sciences
Funding type	Research
Value (£)	262,538
Status	Completed
Type	Research Grant
Start date	01/05/2005
End date	30/04/2009
Duration	48 months

Abstract

Membrane proteins perform a staggering range of biological functions including respiration, signal transduction and molecular transport. The result of various genome projects have shown that up to 30 per cent of proteins encoded by eukaryotic cells are membrane proteins. A more fundamental understanding of the structure-function relationships of membrane proteins would make invaluable contributions to structural biology, pharmacology and medicine. Membrane transport proteins that transduce free energy stored in electrochemical ion gradients into a concentration gradient are a major class of membrane proteins. We have recently report the crystal structure at 3.5 Angstrom of the Escherichia coli lactose permease (LacY), an intensively studied member of the Major Facilitator Superfamily of transporters. A possible mechanism for lactose/proton symport, which includes six different conformational states, was proposed based on the structure and various biochemical/biophysical studies. The X-ray structure only represents one of these six states, namely the protonated inward facing conformation with substrate, and to understand the complete molecular transport mechanism, it is essential to solve the crystal structure of all the rest of the five conformational states. We have recently obtained cystals for two other inward-facing conformational states (deprotonated inward-facing conformation and protonated inward-facing conformation without substrate). The main objectives of this proposal are (1) To solve the structures of deprotonated inward-facing conformation and protonated inward-facing conformation without substrate. (2) To obtain the crystal structures for outward facing conformations using various mutants. (3) To improve the resolution of the LacY structure and reveal the solvent structure in the substrate binding site.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Microbiology, Structural Biology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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