Crystal Structure of Transport Protein Links Structure to Function

Researchers using advanced x-ray crystallography techniques have produced a high-resolution three-dimensional crystal structure for lactose permease, a member of the Major Facilitator Superfamily (MFS) of transport proteins.

Lactose permease is the primary mover of lactose through the membrane of Escherichia coli, and is a model for similar transport proteins in other organisms. By applying the latest x-ray crystallography methods, investigators at Imperial College (London, UK; www.imperial.ac.uk) and the University of California, Los Angeles (USA; www.ucla.edu) have produced the crystal structure at 3.5 angstroms for the E coli lactose permease.

They reported in the August 1, 2003, issue of Science that the molecule was composed of N- and C-terminal domains, each with six transmembrane helices, symmetrically positioned within the permease. A large internal hydrophilic cavity open to the cytoplasmic side represented the inward-facing conformation of the transporter. The structure with a bound lactose homolog, beta-D-galactopyranosyl-1-thio-beta-D-galactopyranoside, revealed the sugar-binding site in the cavity, and residues that play major roles in substrate recognition and proton translocation were identified.

Senior author Professor So Iwata of the laboratory for membrane protein crystallography at Imperial College explained, "The three-dimensional structure of lactose permease gives us our first real picture of how the family of enzymes work. Membrane transport proteins play major roles in depression, stroke and diabetes. Unraveling their structure is critical not only for understanding how we function but also to improve drug design.”





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