Flexibility in the ABC Transporter MsbA: Alternating Access With a Twist
ATP-binding cassette (ABC) transporters are integral membrane proteins that translocate a wide variety of substrates across cellular membranes and are conserved from bacteria to humans. Here we compare four x-ray structures of the bacterial ABC lipid flippase, MsbA, trapped in different conformations, two nucleotide-bound structures and two in the absence of nucleotide. Comparison of the nucleotide-free conformations of MsbA reveals a flexible hinge formed by extracellular loops 2 and 3. This hinge allows the nucleotide-binding domains to disassociate while the ATP-binding half sites remain facing each other. The binding of the nucleotide causes a packing rearrangement of the transmembrane helices and changes the accessibility of the transporter from cytoplasmic (inward) facing to extracellular (outward) facing. The inward and outward openings are mediated by two different sets of transmembrane helix interactions. Altogether, the conformational changes between these structures suggest that large ranges of motion may be required for substrate transport.
- Research Organization:
- Stanford Linear Accelerator Center (SLAC)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC02-76SF00515
- OSTI ID:
- 953902
- Report Number(s):
- SLAC-REPRINT-2009-490
- Journal Information:
- Proc. Nat. Acad. Sci. 104:19005,2007, Journal Name: Proc. Nat. Acad. Sci. 104:19005,2007 Journal Issue: 48 Vol. 104; ISSN 0027-8424; ISSN PNASA6
- Country of Publication:
- United States
- Language:
- English
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