کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1945924 1053280 2007 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Gating of the ATP-sensitive K+ channel by a pore-lining phenylalanine residue
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Gating of the ATP-sensitive K+ channel by a pore-lining phenylalanine residue
چکیده انگلیسی

ATP-sensitive K+ (KATP) channels are gated by intracellular ATP, proton and phospholipids. The pore-forming Kir6.2 subunit has all essential machineries for channel gating by these ligands. It is known that channel gating involves the inner helix bundle of crossing in which a phenylalanine residue (Phe168) is found in the TM2 at the narrowest region of the ion-conduction pathway in the Kir6.2. Here we present evidence that Phe168–Kir6.2 functions as an ATP- and proton-activated gate via steric hindrance and hydrophobic interactions. Site-specific mutations of Phe168 to a small amino acid resulted in losses of the ATP- and proton-dependent gating, whereas the channel gating was well maintained after mutation to a bulky tryptophan, supporting the steric hindrance effect. The steric hindrance effect, though necessary, was insufficient for the gating, as mutating Phe168 to a bulky hydrophilic residue severely compromised the channel gating. Single-channel kinetics of the F168W mutant resembled the wild-type channel. Small residues increased Popen, and displayed long-lasting closures and long-lasting openings. Kinetic modeling showed that these resulted from stabilization of the channel to open and long-lived closed states, suggesting that a bulky and hydrophobic residue may lower the energy barrier for the switch between channel openings and closures. Thus, it is likely that the Phe168 acts as not only a steric hindrance gate but also potentially a facilitator of gating transitions in the Kir6.2 channel.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1768, Issue 1, January 2007, Pages 39–51
نویسندگان
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