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TRANSMEMBRANE HELIX 5
SAFFFSGFFVVFLSVLPYALI
(amino acids 308 thru 328)
The only known high-resolution x-ray crystal structure of an ABC transporter family member is of MsbA. It reveals a central chamber formed within the membrane by contacts between transmembrane helices 2 and 5. This is due the the fact that MsbA, like all bacterial ABC transporters functions as a homodimer (while CFTR functions as a single protein), with TM2 of MsbA contacting TM5 in the opposite half of the protein. These four transmembrane helices can be seen as forming a kind of "hinge" (2 each) on either side of the chamber. All 6 of the transmembrane helices in the MsbA monomer are tilted with respect to the plane of the membrane by between 30 and 40 degrees. It has been predicted by the authors that during gating of MsbA, the transmembrane helices either flip or twist to expose newly accessible areas within the chamber. The transmembrane helix in MsbA which corresponds to CFTR's TM5 are from amino acids 253 to 272. It begins with a kink caused by proline-253. Chang and Roth, Science 293, 9/7/01 pgs 1793-1800.
Point mutations in this helix and helix 6 have been shown to affect anion binding by CFTR. However, permeability ratios of ions was not changed. For this reason, it is believed that anion binding is the process most affected by structural changes. TM5 and 6 are likely to contribute to part of the pore.