1HP2

SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.

Summary for 1HP2

• Entry DOI: 10.2210/pdb1hp2/pdb
• NMR Information: BMRB: 4924
• Descriptor: TITYUSTOXIN K ALPHA (1 entity in total)
• Functional Keywords: k+ channel, scorpion toxin, alpha-k toxin, toxin
• Biological source: Tityus serrulatus (Brazilian scorpion)
• Cellular location: Secreted: P46114
• Total number of polymer chains: 1
• Total formula weight: 3955.84

Authors

Ellis, K.C.,Tenenholz, T.C.,Gilly, W.F.,Blaustein, M.P.,Weber, D.J. (deposition date: 2000-12-12, release date: 2001-06-13, Last modification date: 2024-11-13)

Primary citation

Ellis, K.C.,Tenenholz, T.C.,Jerng, H.,Hayhurst, M.,Dudlak, C.S.,Gilly, W.F.,Blaustein, M.P.,Weber, D.J.
Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A).
Biochemistry, 40:5942-5953, 2001

PubMed Abstract: A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8 ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In both cases, decreasing the pH below 7.0 significantly diminishes the TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH > or =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the three-dimensional structure of TsTX-Kalpha was determined in solution by NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E) significantly reduced the toxin's affinity for sqKv1A channels. This is consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27 of the toxin inserted into the ion conduction pathway of the K(+) channel. This toxin-channel model also illustrates a possible mechanism for the pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23) are repelled by protonated H351 on sqKv1A at low pH.

PubMed: 11352729
DOI: 10.1021/bi010173g

Experimental method

SOLUTION NMR