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Gap junctions are a ubiquitous feature of multicellular life, allowing cells to pass particular classes of biomolecules directly to their neighbors. It is clear that these channels are not just nonspecific pores, but it has been difficult to determine what establishes their specificity. Skerrett et al., whose work appears on page 349, developed a cell perfusion system that allowed them to identify the residues lining an intact gap junction channel. The work helps answer lingering questions about earlier structural models, and identifies some unusual features of gap junctions.
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Previous studies determined the basic structure of a gap junction, in which one membrane-spanning -helix from each subunit of the channel is exposed to the interior of the pore, but this does not reveal what types of residues line the pore or how specificity is determined. The authors generated a panel of mutated connexin proteins, in each case replacing a single amino acid with a cysteine. These altered connexin subunits were expressed in and formed gap junctions between pairs of Xenopus oocytes, and their reactivity with a thiol blocking agent in a novel cell perfusion system pinpointed the residues lining the pore.( n! d6 ^% ?* }& R
5 S V8 D6 I7 ]The results identify a single -helix of the connexin as the main pore-lining segment of the gap junction channel, and suggest that a single face of that helix is exposed to the pore. Surprisingly, the apparent pore-lining residues are almost all hydrophobic, an arrangement that is unique among ion channels studied to date.
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2 G9 I5 n4 H7 ~5 I9 n9 P6 p2 ^7 B; ^+ eSkerrett et al. suggest that, unlike classical ion channels, gap junction channels may interact with passing molecules primarily through hydrophobic and weak forces. The new techniques developed for the study also provide a platform for uncovering other structural details about gap junctions. Recently, for example, the authors have used this strategy to map the location of a gate within the pore.(Mostly hydrophobic residues from a singl) |
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发表于 2009-3-6 00:07
发表于 2015-5-29 16:36
