Visualizing an Intermediate State of the Maltose Transporter
Jue Chen group (Purdue University)
With more than 2000 members identified, ATP-binding cassette
(ABC) transporters are transmembrane proteins that constitute one of the
largest protein superfamilies. They are integral to most biological processes
and many are medically important. ABC transporters function through the
alternating-access model, which is the most general mechanism of membrane
transport. Despite decades of study and recent rapid progress, two
fundamental questions remain unanswered: (1) Do intermediate conformations
exist between the inward- and outward-facing states? (2) How does the
presence of substrate initiate the transport cycle? The Chen group addressed
both of these questions using the maltose transport system of E. coli,
which has long been the prototype for studies of ABC transporters; they
determined the crystal structure of an essential intermediate, the
pretranslocation state, which exists between the inward- and outward-facing
states in the alternating access model. This structure shows that
interactions with the substrate-binding protein prime the transporter for
ATP-induced conformational change by influencing the conformation of the
nucleotide-binding domains on the other side of the membrane.
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Figure: Membrane translocation states of the maltose
transporter – wire representations, and solid representations: MalF
(blue), MBP (lilac), MalG (yellow), MalK (red, green). |
Citation: Oldham ML, Chen J. Crystal Structure of the
Maltose Transporter in a Pretranslocation Intermediate State. Science. 2011
June 3; 332; 1202-5. doi: 10.1126/science.1200767.
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