期刊
JOURNAL OF GENERAL PHYSIOLOGY
卷 130, 期 3, 页码 329-334出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.200709764
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- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL054171] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK069424] Funding Source: NIH RePORTER
- NHLBI NIH HHS [R01 HL054171, HL54171] Funding Source: Medline
- NIDDK NIH HHS [DK69424, R01 DK069424] Funding Source: Medline
Interactions between nontransmembrane domains and the lipid membrane are proposed to modulate activity of many ion channels. In Kir channels, the so-called slide-helix is proposed to interact with the lipid headgroups and control channel gating. We examined this possibility directly in a cell-free system consisting of KirBac1.1 reconstituted into pure lipid vesicles. Cysteine substitution of positively charged slide-helix residues (R49C and K57C) leads to loss of channel activity that is rescued by in situ restoration of charge following modification by MTSET+ or MTSEA(+), but not MTSES- or neutral MMTS. Strikingly, activity is also rescued by modification with long-chain alkyl-MTS reagents. Such reagents are expected to partition into, and hence tether the side chain to, the membrane. Systematic scanning reveals additional slide-helix residues that are activated or inhibited following alkyl-MTS modification. A pattern emerges whereby lipid tethering of the N terminus, or C terminus, of the slide-helix, respectively inhibits, or activates, channel activity. This study establishes a critical role of the slide-helix in Kir channel gating, and directly demonstrates that physical interaction of soluble domains with the membrane can control ion channel activity.
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