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浙江大学学报（医学版）
浙江大学学报（医学版）  2019, Vol. 48 Issue (1): 25-33    DOI: 10.3785/j.issn.1008-9292.2019.02.05
专题报道     
电压门控离子通道结构生物学研究进展
宋方俊1(),郭江涛1,2()
1. 浙江大学医学院生物物理系， 浙江 杭州 310058
2. 浙江大学医学院附属邵逸夫医院病理科， 浙江 杭州 310016
Progress on structural biology of voltage-gated ion channels
SONG Fangjun1(),GUO Hongtao1,2()
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摘要：

离子通道介导离子的跨膜运转，在生物体内的物质交换、能量传递和信号传导过程中发挥关键作用。近年来，离子通道结构生物学研究极大地推动了人们对离子通道的离子选择性和门控机制的认识。电压门控钾通道结构生物学研究阐明了钾离子选择性的结构基础和电压门控机制；电压门控钠通道结构生物学研究揭示了钠通道的慢失活和快失活机制；瞬时受体电位通道结构生物学研究提供了瞬时受体电位通道复杂多样的结构和配体门控机制。本文总结了近年来离子通道结构生物学的研究进展，并展望了未来离子通道结构生物学的发展。
关键词： 离子通道;  蛋白质结构;  离子选择性;  电压门控;  配体门控;  综述    
Abstract:

Ion channels mediate ion transport across membranes, and play vital roles in processes of matter exchange, energy transfer and signal transduction in living organisms. Recently, structural studies of ion channels have greatly advanced our understanding of their ion selectivity and gating mechanisms. Structural studies of voltage-gated potassium channels elucidate the structural basis for potassium selectivity and voltage-gating mechanism; structural studies of voltage-gated sodium channels reveal their slow and fast inactivation mechanisms; and structural studies of transient receptor potential (TRP) channels provide complex and diverse structures of TRP channels, and their ligand gating mechanisms. In the article we summarize recent progress on ion channel structural biology, and outlook the prospect of ion channel structural biology in the future.
Key words: Ion channels    Protein structure    Ionselectivity    Voltage-gating    Ligand-gating    Review
收稿日期: 2018-07-25 出版日期: 2019-05-10
:  Q615  
基金资助: 国家重点研发计划(2018YFA0508100)
通讯作者: 郭江涛     E-mail: fangjun_s@163.com;jiangtaoguo@zju.edu.cn
作者简介: 宋方俊（1996—），男，硕士研究生，主要从事离子通道结构生物学研究；E-mail： fangjun_s@163.com； https://orcid.org/0000-0001-8534-4889|郭江涛（1984—），男，博士，研究员，博士生导师，主要从事离子通道和离子转运蛋白结构生物学研究；E-mail： jiangtaoguo@zju.edu.cn； https://orcid.org/0000-0002-8850-286X
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引用本文:

宋方俊,郭江涛. 电压门控离子通道结构生物学研究进展[J]. 浙江大学学报（医学版）, 2019, 48(1): 25-33.

SONG Fangjun,GUO Hongtao. Progress on structural biology of voltage-gated ion channels. J Zhejiang Univ (Med Sci), 2019, 48(1): 25-33.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.02.05    或    http://www.zjujournals.com/med/CN/Y2019/V48/I1/25

图1  离子通道整体结构示意图
图2  KcsA、NavAb和TRPV6选择性滤器的结构
图3  电压门控钾通道的电压门控机制示意图
通道家族 通道名称 分辨率（nm） 状　态 结合配体或相互作用蛋白 参考文献

电压门控钾通道[border:border-top:solid;]

 KcsA 0.32 关闭态 Apo 1
KvAP 0.32 开放态 Apo 3
Kv1.2 0.29 开放态 氧化还原酶的β亚基 4-5
Kv1.2-2.1 0.24 开放态 嵌合体 6
Eag1 0.38 关闭态 钙调素 7
Slo1.1 0.35 开放态 Apo、钙离子 8-9
hERG1 0.38 开放态 Apo 10
KCNQ1 0.37 关闭态 钙调素 11

电压门控钠通道

 NavAb 0.27～0.32 预开放态、（慢）失活态 Apo，突变体 18, 20
NavRh 0.31 （慢）失活态 Apo 19
NavMs 0.25 开放态 Apo 21
Nav1.7 0.35 失活态 嵌合体，拮抗剂GX-936等 22
NavPaS 0.26～0.38 关闭态 Apo, 河豚毒素, 蛤蚌毒素, 蜘蛛毒素 23-24
EeNav1.4 0.40 开放态 β1亚基 25
Nav1.4 0.32 开放态 β1亚基 26
瞬时受体电位通道 TRPV1 0.38 关闭态、半开放态、开放态 Apo、辣椒素、双结毒素/树脂毒素 29-30
TRPA1 约0.40 关闭态 Apo、拮抗剂A-967079 32
TRPV2 0.31～0.50 关闭态、开放态 Apo、钙离子、树脂毒素 33-35
TRPV4 0.38 关闭态 Apo 36
TRPV5 0.48 关闭态 拮抗剂益康唑 37
TRPV6 0.33～0.40 关闭态、开放态 Apo，突变体 38-39
TRPP2 0.30～0.43 关闭态 Apo 40-42
TRPML1 0.35～0.37 关闭态、开放态 Apo、激动剂ML-SA1 43-44
TRPML3 0.29 关闭态 Apo 45
TRPM2 0.30～0.38 关闭态 钙离子，二磷酸腺苷核糖 46-47
TRPM4 0.29～0.38 关闭态 ATP、钙离子、十钒酸 48-51
TRPM8 0.41 未知 Apo 52
TRPC3 0.33～0.44 关闭态 Apo 53-54
TRPC4 0.33～0.36 关闭态 Apo 55-56
TRPC6 0.38 关闭态 抑制剂BTDM 53
NOMPC 0.36 关闭态 Apo 57
PKD2L1 0.34 开放态 Apo 58-59
表1  已知电压门控钾通道、电压门控钠通道、瞬时受体电位通道结构一览
图4  TRPML1的配体门控机制示意图
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