Metal-binding Dependent Disruption of Membranes by Designed Helices

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2009 Feb 13

PMID 19209932

Citations 11

Authors

Rachel S Signarvic

William F DeGrado

Affiliations

Soon will be listed here.

Abstract

The de novo design of molecular switching peptides is of increasing interest because it tests and extends our fundamental understanding of this process while laying the groundwork for the creation of new chemical and biological sensors. Here, an alpha-helical amphiphilic cell-lytic peptide, mastoparan X, was engineered to bind divalent cations. Binding of Zn(II) or Ni(II) to the designed peptide Mst-HH stabilizes the lytic amphiphilic structure and increases the activity of the peptide. Although both Zn(II) and Ni(II) activate Mst-HH for membrane lysis, they appear to do so via different mechanisms. Additionally, a series of metal binding-site mutants were synthesized to assess the relationship of charge and helical propensity to the toxicity and switchability. Additionally, by changing the characteristics of the metal-binding ligands, we can vary the selectivity of the site.

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References

Calhoun J, Kono H, Lahr S, Wang W, DeGrado W, Saven J . Computational design and characterization of a monomeric helical dinuclear metalloprotein. J Mol Biol. 2003; 334(5):1101-15. DOI: 10.1016/j.jmb.2003.10.004. View

Higashijima T, Wakamatsu K, Takemitsu M, Fujino M, Nakajima T, Miyazawa T . Conformational change of mastoparan from wasp venom on binding with phospholipid membrane. FEBS Lett. 1983; 152(2):227-30. DOI: 10.1016/0014-5793(83)80385-8. View

Maloy W, Kari U . Structure-activity studies on magainins and other host defense peptides. Biopolymers. 1995; 37(2):105-22. DOI: 10.1002/bip.360370206. View

Abraham T, Marwaha S, Kobewka D, Lewis R, Prenner E, Hodges R . The relationship between the binding to and permeabilization of phospholipid bilayer membranes by GS14dK4, a designed analog of the antimicrobial peptide gramicidin S. Biochim Biophys Acta. 2007; 1768(9):2089-98. PMC: 3251618. DOI: 10.1016/j.bbamem.2007.06.023. View

Farrer B, Pecoraro V . Hg(II) binding to a weakly associated coiled coil nucleates an encoded metalloprotein fold: a kinetic analysis. Proc Natl Acad Sci U S A. 2003; 100(7):3760-5. PMC: 152995. DOI: 10.1073/pnas.0336055100. View

Mendes M, de Souza B, Marques M, Palma M . Structural and biological characterization of two novel peptides from the venom of the neotropical social wasp Agelaia pallipes pallipes. Toxicon. 2004; 44(1):67-74. DOI: 10.1016/j.toxicon.2004.04.009. View

Calhoun J, Nastri F, Maglio O, Pavone V, Lombardi A, DeGrado W . Artificial diiron proteins: from structure to function. Biopolymers. 2005; 80(2-3):264-78. DOI: 10.1002/bip.20230. View

Frecer V . QSAR analysis of antimicrobial and haemolytic effects of cyclic cationic antimicrobial peptides derived from protegrin-1. Bioorg Med Chem. 2006; 14(17):6065-74. DOI: 10.1016/j.bmc.2006.05.005. View

Ulrich A, Otter M, Glabe C, Hoekstra D . Membrane fusion is induced by a distinct peptide sequence of the sea urchin fertilization protein bindin. J Biol Chem. 1998; 273(27):16748-55. DOI: 10.1074/jbc.273.27.16748. View

10.

Degrado W . Design of peptides and proteins. Adv Protein Chem. 1988; 39:51-124. DOI: 10.1016/s0065-3233(08)60375-7. View

11.

Tang J, Signarvic R, DeGrado W, Gai F . Role of helix nucleation in the kinetics of binding of mastoparan X to phospholipid bilayers. Biochemistry. 2007; 46(48):13856-63. DOI: 10.1021/bi7018404. View

12.

Schwarz G, Reiter R . Negative cooperativity and aggregation in biphasic binding of mastoparan X peptide to membranes with acidic lipids. Biophys Chem. 2001; 90(3):269-77. DOI: 10.1016/s0301-4622(01)00149-1. View

13.

Degrado W, Musso G, Lieber M, Kaiser E, Kezdy F . Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophys J. 1982; 37(1):329-38. PMC: 1329147. DOI: 10.1016/S0006-3495(82)84681-X. View

14.

Ambroggio X, Kuhlman B . Computational design of a single amino acid sequence that can switch between two distinct protein folds. J Am Chem Soc. 2006; 128(4):1154-61. DOI: 10.1021/ja054718w. View

15.

Scholtz J, Barrick D, York E, Stewart J, Baldwin R . Urea unfolding of peptide helices as a model for interpreting protein unfolding. Proc Natl Acad Sci U S A. 1995; 92(1):185-9. PMC: 42842. DOI: 10.1073/pnas.92.1.185. View

16.

Chen Y, Mant C, Farmer S, Hancock R, Vasil M, Hodges R . Rational design of alpha-helical antimicrobial peptides with enhanced activities and specificity/therapeutic index. J Biol Chem. 2005; 280(13):12316-29. PMC: 1393284. DOI: 10.1074/jbc.M413406200. View

17.

Ghosh D, Pecoraro V . Understanding metalloprotein folding using a de novo design strategy. Inorg Chem. 2004; 43(25):7902-15. DOI: 10.1021/ic048939z. View

18.

Tamba Y, Yamazaki M . Single giant unilamellar vesicle method reveals effect of antimicrobial peptide magainin 2 on membrane permeability. Biochemistry. 2005; 44(48):15823-33. DOI: 10.1021/bi051684w. View

19.

Tossi A, Sandri L, Giangaspero A . Amphipathic, alpha-helical antimicrobial peptides. Biopolymers. 2000; 55(1):4-30. DOI: 10.1002/1097-0282(2000)55:1<4::AID-BIP30>3.0.CO;2-M. View

20.

van den Bogaart G, Velasquez Guzman J, Mika J, Poolman B . On the mechanism of pore formation by melittin. J Biol Chem. 2008; 283(49):33854-7. PMC: 2662212. DOI: 10.1074/jbc.M805171200. View