Metal-assisted Channel Stabilization: Disposition of a Single Histidine on the N-terminus of Alamethicin Yields Channels with Extraordinarily Long Lifetimes

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 2010 May 6

PMID 20441743

Citations 2

Authors

Daisuke Noshiro

Koji Asami

Shiroh Futaki

Affiliations

Soon will be listed here.

Abstract

Alamethicin, a member of the peptaibol family of antibiotics, is a typical channel-forming peptide with a helical structure. The self-assembly of the peptide in the membranes yields voltage-dependent channels. In this study, three alamethicin analogs possessing a charged residue (His, Lys, or Glu) on their N-termini were designed with the expectation of stabilizing the transmembrane structure. A slight elongation of channel lifetime was observed for the Lys and Glu analogs. On the other hand, extensive stabilization of certain channel open states was observed for the His analog. This stabilization was predominantly observed in the presence of metal ions such as Zn(2+), suggesting that metal coordination with His facilitates the formation of a supramolecular assembly in the membranes. Channel stability was greatly diminished by acetylation of the N-terminal amino group, indicating that the N-terminal amino group also plays an important role in metal coordination.

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References

Duclohier H, Molle G, Dugast J, SPACH G . Prolines are not essential residues in the "barrel-stave" model for ion channels induced by alamethicin analogues. Biophys J. 1992; 63(3):868-73. PMC: 1262221. DOI: 10.1016/S0006-3495(92)81637-5. View

Sakoh M, Okazaki T, Nagaoka Y, Asami K . N-terminal insertion of alamethicin in channel formation studied using its covalent dimer N-terminally linked by disulfide bond. Biochim Biophys Acta. 2003; 1612(1):117-21. DOI: 10.1016/s0005-2736(03)00110-x. View

Gschwind A, Fischer O, Ullrich A . The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004; 4(5):361-70. DOI: 10.1038/nrc1360. View

Futaki S . Peptide ion channels: design and creation of function. Biopolymers. 1998; 47(1):75-81. DOI: 10.1002/(SICI)1097-0282(1998)47:1<75::AID-BIP8>3.0.CO;2-U. View

Woolley G, Biggin P, Schultz A, Lien L, Jaikaran D, Breed J . Intrinsic rectification of ion flux in alamethicin channels: studies with an alamethicin dimer. Biophys J. 1997; 73(2):770-8. PMC: 1180973. DOI: 10.1016/S0006-3495(97)78109-8. View

Fox Jr R, Richards F . A voltage-gated ion channel model inferred from the crystal structure of alamethicin at 1.5-A resolution. Nature. 1982; 300(5890):325-30. DOI: 10.1038/300325a0. View

Bayley H, Jayasinghe L . Functional engineered channels and pores (Review). Mol Membr Biol. 2004; 21(4):209-20. DOI: 10.1080/09687680410001716853. View

Futaki S, Fukuda M, Omote M, Yamauchi K, Yagami T, Niwa M . Alamethicin-leucine zipper hybrid peptide: a prototype for the design of artificial receptors and ion channels. J Am Chem Soc. 2001; 123(49):12127-34. DOI: 10.1021/ja011166i. View

Singer S . The structure and insertion of integral proteins in membranes. Annu Rev Cell Biol. 1990; 6:247-96. DOI: 10.1146/annurev.cb.06.110190.001335. View

10.

Sakai N, Mareda J, Matile S . Rigid-rod molecules in biomembrane models: from hydrogen-bonded chains to synthetic multifunctional pores. Acc Chem Res. 2005; 38(2):79-87. DOI: 10.1021/ar0400802. View

11.

Duclohier H, Kociolek K, Stasiak M, Leplawy M, Marshall G . C-terminally shortened alamethicin on templates: influence of the linkers on conductances. Biochim Biophys Acta. 1999; 1420(1-2):14-22. DOI: 10.1016/s0005-2736(99)00047-4. View

12.

Trudell J, Yue M, Bertaccini E, Jenkins A, Harrison N . Molecular modeling and mutagenesis reveals a tetradentate binding site for Zn2+ in GABA(A) alphabeta receptors and provides a structural basis for the modulating effect of the gamma subunit. J Chem Inf Model. 2008; 48(2):344-9. DOI: 10.1021/ci700324a. View

13.

Futaki S, Asami K . Ligand-induced extramembrane conformation switch controlling alamethicin assembly and the channel current. Chem Biodivers. 2007; 4(6):1313-22. DOI: 10.1002/cbdv.200790112. View

14.

You S, Peng S, Lien L, Breed J, Sansom M, Woolley G . Engineering stabilized ion channels: covalent dimers of alamethicin. Biochemistry. 1996; 35(20):6225-32. DOI: 10.1021/bi9529216. View

15.

Borisenko V, Zhang Z, Woolley G . Gramicidin derivatives as membrane-based pH sensors. Biochim Biophys Acta. 2001; 1558(1):26-33. DOI: 10.1016/s0005-2736(01)00415-1. View

16.

Kiwada T, Sonomura K, Sugiura Y, Asami K, Futaki S . Transmission of extramembrane conformational change into current: construction of metal-gated ion channel. J Am Chem Soc. 2006; 128(18):6010-1. DOI: 10.1021/ja060515b. View

17.

Futaki S, Zhang Y, Kiwada T, Nakase I, Yagami T, Oiki S . Gramicidin-based channel systems for the detection of protein-ligand interaction. Bioorg Med Chem. 2004; 12(6):1343-50. DOI: 10.1016/j.bmc.2003.06.003. View

18.

SCHMITT J, Sansom M, Kerr I, Lunt G, Eisenthal R . Ferrocenoyl derivatives of alamethicin: redox-sensitive ion channels. Biochemistry. 1997; 36(5):1115-22. DOI: 10.1021/bi962168w. View

19.

Capone R, Blake S, Restrepo M, Yang J, Mayer M . Designing nanosensors based on charged derivatives of gramicidin A. J Am Chem Soc. 2007; 129(31):9737-45. DOI: 10.1021/ja0711819. View

20.

Woolley G, Epand R, Kerr I, Sansom M, Wallace B . Alamethicin pyromellitate: an ion-activated channel-forming peptide. Biochemistry. 1994; 33(22):6850-8. DOI: 10.1021/bi00188a014. View