C-Terminal residues in small potassium channel blockers OdK1 and OSK3 from scorpion venom fine-tune the selectivity

被引：6
作者：
Kuzmenkov, Alexey I. [1 ,2 ]
Peigneur, Steve [3 ]
Chugunov, Anton O. [1 ,4 ]
Tabakmakher, Valentin M. [1 ]
Efremov, Roman G. [1 ,4 ]
Tytgat, Jan [3 ]
Grishin, Eugene V. [1 ]
Vassilevski, Alexander A. [1 ,2 ]
机构：
[1] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia
[2] Lomonosov Moscow State Univ, Biol Fac, Moscow 119992, Russia
[3] Univ Leuven, Toxicol & Pharmacol, B-3000 Louvain, Belgium
[4] Natl Res Univ, Higher Sch Econ, Moscow 101000, Russia
来源：
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2017年 / 1865卷 / 05期
基金：
俄罗斯科学基金会;
关键词：
Scorpion toxins; Voltage-gated potassium channels; Pore blockers; Cysteine-stabilized alpha/beta fold (CS alpha/beta); KTx; KV1.3; CHANNEL; THERAPEUTIC TARGET; K+ CHANNELS; TOXIN; PEPTIDE; PURIFICATION; SPECIFICITY; SIMULATIONS; INHIBITOR; PROTEIN;
D O I：
10.1016/j.bbapap.2017.02.001
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We report isolation, sequencing, and electrophysiological characterization of OSK3 (alpha-KTx 8.8 in Kalium and Uniprot databases), a potassium channel blocker from the scorpion Orthochirus scrobiculosus venom. Using the voltage clamp technique, OSK3 was tested on a wide panel of 11 voltage-gated potassium channels expressed in Xenopus oocytes, and was found to potently inhibit Kv1.2 and Kv1.3 with IC50 values of similar to 331 nM and similar to 503 nM, respectively. OdK1 produced by the scorpion Odontobuthus doriae differs by just two C-terminal residues from OSK3, but shows marked preference to Kv1.2. Based on the charybdotoxin-potassium channel complex crystal structure, a model was built to explain the role of the variable residues in OdK1 and OSK3 selectivity. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码：465 / 472
页数：8
相关论文
共 51 条
  • [1] The first potassium channel toxin from the venom of the Iranian scorpion Odonthobuthus doriae
    Abdel-Mottaleb, Yousra
    Clynen, Elke
    Jalali, Amir
    Bosmans, Frank
    Vatanpour, Hossein
    Schoofs, Liliane
    Tytgat, Jan
    [J]. FEBS LETTERS, 2006, 580 (26) : 6254 - 6258
  • [2] Venom proteomic and venomous glands transcriptomic analysis of the Egyptian scorpion Scorpio maurus palmatus (Arachnida: Scorpionidae)
    Abdel-Rahman, Mohamed A.
    Quintero-Hernandez, Veronica
    Possani, Lourival D.
    [J]. TOXICON, 2013, 74 : 193 - 207
  • [3] Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers
    Abraham, Mark James
    Murtola, Teemu
    Schulz, Roland
    Páll, Szilárd
    Smith, Jeremy C.
    Hess, Berk
    Lindah, Erik
    [J]. SoftwareX, 2015, 1-2 : 19 - 25
  • [4] Sequence-specific determination of protein and peptide concentrations by absorbance at 205 nm
    Anthis, Nicholas J.
    Clore, G. Marius
    [J]. PROTEIN SCIENCE, 2013, 22 (06) : 851 - 858
  • [5] Structure of a pore-blocking toxin in complex with a eukaryotic voltage-dependent K+ channel
    Banerjee, Anirban
    Lee, Alice
    Campbell, Ernest
    MacKinnon, Roderick
    [J]. ELIFE, 2013, 2
  • [6] Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases
    Beeton, Christine
    Wulff, Heike
    Standifer, Nathan E.
    Azam, Philippe
    Mullen, Katherine M.
    Pennington, Michael W.
    Kolski-Andreaco, Aaron
    Wei, Eric
    Grino, Alexandra
    Counts, Debra R.
    Wang, Ping H.
    LeeHealey, Christine J.
    Andrews, Brian S.
    Sankaranarayanan, Ananthakrishnan
    Homerick, Daniel
    Roeck, Werner W.
    Tehranzadeh, Jamshid
    Stanhope, Kimber L.
    Zimin, Pavel
    Havel, Peter J.
    Griffey, Stephen
    Knaus, Hans-Guenther
    Nepom, Gerald T.
    Gutman, George A.
    Calabresi, Peter A.
    Chandy, K. George
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (46) : 17414 - 17419
  • [7] Unique Bell-shaped Voltage-dependent Modulation of Na+ Channel Gating by Novel Insect-selective Toxins from the Spider Agelena orientalis
    Billen, Bert
    Vassilevski, Alexander
    Nikolsky, Anton
    Debaveye, Sarah
    Tytgat, Jan
    Grishin, Eugene
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (24) : 18545 - 18554
  • [8] Blanc E, 1996, PROTEINS, V24, P359, DOI 10.1002/(SICI)1097-0134(199603)24:3<359::AID-PROT9>3.0.CO
  • [9] 2-B
  • [10] N-terminally extended analogues of the K+ channel toxin from Stichodactyla helianthus as potent and selective blockers of the voltage-gated potassium channel Kv1.3
    Chang, Shih C.
    Huq, Redwan
    Chhabra, Sandeep
    Beeton, Christine
    Pennington, Michael W.
    Smith, Brian J.
    Norton, Raymond S.
    [J]. FEBS JOURNAL, 2015, 282 (12) : 2247 - 2259
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