Cooperative helix stabilization by complex Arg-Glu salt bridges

C. Anders Olson, Erik J. Spek, Zhengshuang Shi, Alexander Vologodskii, Neville R. Kallenbach

Research output: Contribution to journalArticle

Abstract

Among the interactions that stabilize the native state of proteins, the role of electrostatic interactions has been difficult to quantify precisely. Surface salt bridges or ion pairs between acidic and basic side chains have only a modest stabilizing effect on the stability of helical peptides or proteins: estimates are roughly 0.5 kcal/mol or less. On the other hand, theoretical arguments and the occurrence of salt bridge networks in thermophilic proteins suggest that multiple salt bridges may exert a stronger stabilizing effect. We show here that triads of charged side chains, Arg+-Glu-Arg+ spaced at i,i+4 or i,i+3 intervals in a helical peptide stabilize alpha helix by more than the additive contribution of two single salt bridges. The free energy of the triad is more than 1 kcal/mol in excess of the sum of the individual pairs, measured in low salt concentration (10 mM). The effect of spacing the three groups is severe; placing the charges at i,i+4 or i,i+3 sites has a strong effect on stability relative to single bridges; other combinations are weaker. A conservative calculation suggests that interactions of this kind between salt bridges can account for much of the stabilization of certain thermophilic proteins.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalProteins: Structure, Function and Genetics
Volume44
Issue number2
DOIs
StatePublished - Aug 1 2001

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arginine glutamate
Stabilization
Salts
Proteins
Peptides
Coulomb interactions
Static Electricity
Free energy
Ions

ASJC Scopus subject areas

  • Genetics
  • Structural Biology
  • Biochemistry

Cite this

Olson, C. A., Spek, E. J., Shi, Z., Vologodskii, A., & Kallenbach, N. R. (2001). Cooperative helix stabilization by complex Arg-Glu salt bridges. Proteins: Structure, Function and Genetics, 44(2), 123-132. https://doi.org/10.1002/prot.1079

Cooperative helix stabilization by complex Arg-Glu salt bridges. / Olson, C. Anders; Spek, Erik J.; Shi, Zhengshuang; Vologodskii, Alexander; Kallenbach, Neville R.

In: Proteins: Structure, Function and Genetics, Vol. 44, No. 2, 01.08.2001, p. 123-132.

Research output: Contribution to journalArticle

Olson, CA, Spek, EJ, Shi, Z, Vologodskii, A & Kallenbach, NR 2001, 'Cooperative helix stabilization by complex Arg-Glu salt bridges', Proteins: Structure, Function and Genetics, vol. 44, no. 2, pp. 123-132. https://doi.org/10.1002/prot.1079
Olson, C. Anders ; Spek, Erik J. ; Shi, Zhengshuang ; Vologodskii, Alexander ; Kallenbach, Neville R. / Cooperative helix stabilization by complex Arg-Glu salt bridges. In: Proteins: Structure, Function and Genetics. 2001 ; Vol. 44, No. 2. pp. 123-132.
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