2MVT

Solution structure of scoloptoxin SSD609 from Scolopendra mutilans

Summary for 2MVT

• Entry DOI: 10.2210/pdb2mvt/pdb
• NMR Information: BMRB: 25283
• Descriptor: Scoloptoxin SSD609 (1 entity in total)
• Functional Keywords: toxin
• Biological source: Scolopendra mutilans
• Total number of polymer chains: 1
• Total formula weight: 5640.35

Authors

Wu, F.,Sun, P.,Wang, C.,He, Y.,Zhang, L.,Tian, C. (deposition date: 2014-10-14, release date: 2015-09-23, Last modification date: 2024-11-06)

Primary citation

Sun, P.,Wu, F.,Wen, M.,Yang, X.,Wang, C.,Li, Y.,He, S.,Zhang, L.,Zhang, Y.,Tian, C.
A distinct three-helix centipede toxin SSD609 inhibits Iks channels by interacting with the KCNE1 auxiliary subunit.
Sci Rep, 5:13399-13399, 2015

PubMed Abstract: KCNE1 is a single-span transmembrane auxiliary protein that modulates the voltage-gated potassium channel KCNQ1. The KCNQ1/KCNE1 complex in cardiomyocytes exhibited slow activated potassium (I(ks)) currents. Recently, a novel 47-residue polypeptide toxin SSD609 was purified from Scolopendra subspinipes dehaani venom and showed I(ks) current inhibition. Here, chemically synthesized SSD609 was shown to exert I(ks) inhibition in extracted guinea pig cardiomyocytes and KCNQ1/KCNE1 current attenuation in CHO cells. The K(+) current attenuation of SSD609 showed decent selectivity among different auxiliary subunits. Solution nuclear magnetic resonance analysis of SSD609 revealed a distinctive three-helix conformation that was stabilized by a new disulfide bonding pattern as well as segregated surface charge distribution. Structure-activity studies demonstrated that negatively charged Glu19 in the amphipathic extracellular helix of KCNE1 was the key residue that interacted with SSD609. The distinctive three-helix centipede toxin SSD609 is known to be the first polypeptide toxin acting on channel auxiliary subunit KCNE1, which suggests a new type of pharmacological regulation for ion channels in cardiomyocytes.

PubMed: 26307551
DOI: 10.1038/srep13399

Experimental method

SOLUTION NMR