Structural and functional analysis of natrin, a venom protein that targets various ion channels.
Cysteine-rich secretory proteins (CRISPs) are secreted single-chain proteins found in different sources. Natrin is a member of the CRISP family purified from the snake venom of Naja naja atra, which has been reported as a BKca channel blocker. In our study, crystals of natrin were obtained in two different crystal forms and the structure of one of them was solved at a resolution of 1.68A. Our electrophysiological experiments indicated that natrin can block the ion channel currents of the voltage-gated potassium channel Kv1.3. Docking analyses of the interaction between natrin and Kv1.3 revealed a novel interaction pattern different from the two previously reported K(+) channel inhibition models termed "functional dyad" and "basic ring". These findings offered new insights into the function of natrin and how the specific interactions between CRISPs and different ion channels can be achieved.
Wang
Feng
F
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
Li
He
H
Liu
Ming-na
MN
Song
Hui
H
Han
Hong-mei
HM
Wang
Qiong-ling
QL
Yin
Chang-chen
CC
Zhou
Yuan-cong
YC
Qi
Zhi
Z
Shu
Yu-yan
YY
Lin
Zheng-jiong
ZJ
Jiang
Tao
T
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004546:Elapid Venoms / Q000737:chemistry* / Q000378:metabolism; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D004546:Elapid Venoms; D051664:Kv1.3 Potassium Channel; C495581:natrin protein, Naja atra