Solution Structure for Pandinus Toxin K- (PiTX-K), a Sele
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- 作者：T. C. Tenenholz ; R. S. Rogowski ; J. H. Collins ; M. P. Blaustein ; and D. J. Weber
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：March 11, 1997
- 年：1997
- 卷：36
- 期：10
- 页码：2763 - 2771
- 全文大小：234K
- 年卷期：v.36,no.10(March 11, 1997)
- ISSN：1520-4995
文摘
PiTX-KMG SRC="/images/gifchars/alpha.gif" BORDER=0>, a 35-residue peptide recently isolated from the venomof Pandinus imperator, blocksthe rapidly inactivating (A-type) K+ channel(s) inrat brain synaptosomes and the cloned Kv1.2 potassiumchannel at very low toxin concentrations (6 nM and 32 pM, respectively)[Rogowski, R. S., Collins, J.H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A.,Tenenholz, T. C., Weber, D. J.,& Blaustein, M. P. (1996) Mol. Pharmacol. 50,1167-1177]. The three-dimensional structure ofPiTX-K
mages/gifchars/alpha.gif" BORDER=0> was determined using NMR spectroscopy in order to understand itsselectivity and affinity towardK+ channels. PiTX-Kmages/gifchars/alpha.gif" BORDER=0> was found to have anmages/gifchars/alpha.gif" BORDER=0>-helix from residues 10 to 21 and two mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strands(mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">I,26-28; mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">II, 33-35) connected by a type II mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-turn to form asmall antiparallel mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet. Three disulfidebonds, which are conserved in all members of the charybdotoxin family(mages/gifchars/alpha.gif" BORDER=0>-K toxins), anchor one face ofthe mages/gifchars/alpha.gif" BORDER=0>-helix to the mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-sheet. The N-terminal portion ofPiTX-Kmages/gifchars/alpha.gif" BORDER=0> has three fewer residues than other mages/gifchars/alpha.gif" BORDER=0>-Ktoxins such as charybdotoxin. Rather than forming a thirdmages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strand as found for other mages/gifchars/alpha.gif" BORDER=0>-K toxins, theN-terminal region of PiTX-Kmages/gifchars/alpha.gif" BORDER=0> adopts an extended conformation.This structural difference in PiTX-Kmages/gifchars/alpha.gif" BORDER=0>together with differences in sequence at Pro-10, Tyr-14, and Asn-25(versus Ser-10, Trp-14, and Arg-25in CTX) may explain why PiTX-Kmages/gifchars/alpha.gif" BORDER=0> does not block maxi-K+channels. Differences in three-dimensionalstructure between PiTX-Kmages/gifchars/alpha.gif" BORDER=0> and charybdotoxin are also observed in boththe tight turn and the loop thatconnects the first mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-strand to the mages/gifchars/alpha.gif" BORDER=0>-helix. As a result, sidechains of two residues (Tyr-23 and Arg-31)are in regions of PiTX-Kmages/gifchars/alpha.gif" BORDER=0> that probably interact with rapidlyinactivating A-type K+ channels. Theanalogous residues in charybdotoxin are positioned differently on thetoxin surface. Thus, the locationsof Tyr-23 and Arg-31 side chains in PiTX-Kmages/gifchars/alpha.gif" BORDER=0> could explain why thistoxin blocks A-type channels atmuch lower concentrations than does charybdotoxin.