The cytoplasmic coiled-coil mediates cooperative gating temperature sensitivity in the voltage-gated H+ channel Hv1

被引：91

作者：

Fujiwara, Yuichiro ^{[1
,2
]}

Kurokawa, Tatsuki ^{[1
,2
]}

Takeshita, Kohei ^{[3
]}

Kobayashi, Megumi ^{[1
,2
]}

Okochi, Yoshifumi ^{[1
,2
]}

Nakagawa, Atsushi ^{[3
,4
]}

Okamura, Yasushi ^{[1
,2
,4
]}

机构：

[1] Osaka Univ, Grad Sch, Dept Physiol, Lab Integrat Physiol, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Fac Med, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Inst Prot Res, Lab Supramol Crystallog, Res Ctr State Of The Art Funct Prot Anal, Suita, Osaka 5650871, Japan

[4] Osaka Univ, Grad Sch Frontier Biosci, Osaka, Japan

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

关键词：

PROTON CHANNEL; POTASSIUM CHANNEL; CRYSTAL-STRUCTURE; TETRAMERIZATION DOMAIN; SUBUNIT STOICHIOMETRY; HUMAN NEUTROPHILS; ION CHANNELS; PORES; PROTEIN; SENSOR;

D O I：

10.1038/ncomms1823

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hv1/VSOP is a dimeric voltage-gated H+ channel in which the gating of one subunit is reportedly coupled to that of the other subunit within the dimer. The molecular basis for dimer formation and intersubunit coupling, however, remains unknown. Here we show that the carboxy terminus ends downstream of the S4 voltage-sensor helix twist in a dimer coiled-coil architecture, which mediates cooperative gating. We also show that the temperature-dependent activation of H+ current through Hv1/VSOP is regulated by thermostability of the coiled-coil domain, and that this regulation is altered by mutation of the linker between S4 and the coiled-coil. Cooperative gating within the dimer is also dependent on the linker structure, which circular dichroism spectrum analysis suggests is alpha-helical. Our results indicate that the cytoplasmic coiled-coil strands form continuous alpha-helices with S4 and mediate cooperative gating to adjust the range of temperatures over which Hv1/VSOP operates.

引用

页数：11

共 54 条

[1] A heterodimerizing leucine zipper coiled coil system for examining the specificity of a position interactions: Amino acids I, V, L, N, A, and K [J].