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TRANSMEMBRANE HELIX 2
SIAIYLGIGLCLLFIVRTLLL
(amino acids 118 thru 138)
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 corresponding to CFTR's TM2 are the amino acids 22 thru 52. Chang and Roth, Science 293, 9/7/01 pgs 1793-1800.
In the ligand-gated chloride channels GABA(A) and glycine, transmembrane helix 2 has been shown to line the pore. In CFTR, it still isn't known which helix or helices contribute, although mutagenesis has suggested helices 1, 5, 6 and 12 contribute at least some residues. There is additional evidence this helix does as well. An experiment was performed where artificial peptides were made based on the sequence of the amino acids in this as well as helix 6. These were then incorporated into lipid bilayers and CFTR-like pores were formed.
There are 6 positively charged amino acid residues in the transmembrane helices of CFTR (K95 in M1, R134 in M2, R334 and K335 as well as R347 in M6, R1030 in M10) and they seem to be highly conserved between species.