Solution structure of extracellular loop of human β4 subunit of BK channel and its biological implication on ChTX sensitivity.
Solution structure of extracellular loop of human β4 subunit of BK channel and its biological implication on ChTX sensitivity.
复制标题
BK通道β4亚基胞外环的溶液结构及其对ChTX敏感性的生物学意义
DOI：
10.1038/s41598-018-23016-y
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发表时间：
2018-03-15
影响因子：
4.6
通讯作者：
Cao C
中科院分区：
文献类型：
--
作者：
Wang Y;Lan W;Yan Z;Gao J;Liu X;Wang S;Guo X;Wang C;Zhou H;Ding J;Cao C
Large-conductance Ca2+- and voltage-dependent K+ (BK) channels display diverse biological functions while their pore-forming α subunit is coded by a single Slo1 gene. The variety of BK channels is correlated with the effects of BKα coexpression with auxiliary β (β1-β4) subunits, as well as newly defined γ subunits. Charybdotoxin (ChTX) blocks BK channel through physically occluding the K+-conduction pore. Human brain enriched β4 subunit (hβ4) alters the conductance-voltage curve, slows activation and deactivation time courses of BK channels. Its extracellular loop (hβ4-loop) specifically impedes ChTX to bind BK channel pore. However, the structure of β4 subunit’s extracellular loop and the molecular mechanism for gating kinetics, toxin sensitivity of BK channels regulated by β4 are still unclear. To address them, here, we first identified four disulfide bonds in hβ4-loop by mass spectroscopy and NMR techniques. Then we determined its three-dimensional solution structure, performed NMR titration and electrophysiological analysis, and found that residue Asn123 of β4 subunit regulated the gating and pharmacological characteristics of BK channel. Finally, by constructing structure models of BKα/β4 and thermodynamic double-mutant cycle analysis, we proposed that BKα subunit might interact with β4 subunit through the conserved residue Glu264(BKα) coupling with residue Asn123(β4).
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影响因子：
--
作者：
Li Q;Yan J
通讯作者：
Yan J
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1152/nips.01387.2002
发表时间：
2002-08-01
期刊：
NEWS IN PHYSIOLOGICAL SCIENCES
影响因子：
--
作者：
Orio, P;Rojas, P;Latorre, R
通讯作者：
Latorre, R
影响因子：
2.4
作者：
Lippiat, JD;Standen, NB;Davies, NW
通讯作者：
Davies, NW
DOI：
10.1073/pnas.1216953109
发表时间：
2012-11-13
影响因子：
11.1
作者：
Contreras, Gustavo F.;Neely, Alan;Latorre, Ramon
通讯作者：
Latorre, Ramon