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Packing and hydrophobicity effects on protein folding and stability: effects of beta-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers.
Protein Sci. 1993 Mar; 2(3):383-94.PS

Abstract

The aim of this study was to examine the differences between hydrophobicity and packing effects in specifying the three-dimensional structure and stability of proteins when mutating hydrophobes in the hydrophobic core. In DNA-binding proteins (leucine zippers), Leu residues are conserved at positions "d," and beta-branched amino acids, Ile and Val, often occur at positions "a" in the hydrophobic core. In order to discern what effect this selective distribution of hydrophobes has on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers, three Val or three Ile residues were simultaneously substituted for Leu at either positions "a" (9, 16, and 23) or "d" (12, 19, and 26) in both chains of a model coiled coil. The stability of the resulting coiled coils was monitored by CD in the presence of Gdn.HCl. The results of the mutations of Ile to Val at either positions "a" or "d" in the reduced or oxidized coiled coils showed a significant hydrophobic effect with the additional methylene group in Ile stabilizing the coiled coil (delta delta G values range from 0.45 to 0.88 kcal/mol/mutation). The results of mutations of Leu to Ile or Val at positions "a" in the reduced or oxidized coiled coils showed a significant packing effect in stabilizing the coiled coil (delta delta G values range from 0.59 to 1.03 kcal/mol/mutation). Our results also indicate the subtle control hydrophobic packing can have not only on protein stability but on the conformation adopted by the amphipathic alpha-helices. These structural findings correlate with the observation that in DNA-binding proteins, the conserved Leu residues at positions "d" are generally less tolerant of amino acid substitutions than the hydrophobic residues at positions "a."

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Authors+Show Affiliations

Zhu BY
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Zhou NE
No affiliation info available
Kay CM
No affiliation info available
Hodges RS
No affiliation info available

MeSH

Amino Acid SequenceDNA-Binding ProteinsDrug DesignDrug StabilityIsoleucineLeucine ZippersMolecular Sequence DataProtein DenaturationProtein FoldingProtein Structure, SecondaryProteinsValine

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8453376

Citation

Zhu, B Y., et al. "Packing and Hydrophobicity Effects On Protein Folding and Stability: Effects of Beta-branched Amino Acids, Valine and Isoleucine, On the Formation and Stability of Two-stranded Alpha-helical Coiled Coils/leucine Zippers." Protein Science : a Publication of the Protein Society, vol. 2, no. 3, 1993, pp. 383-94.
Zhu BY, Zhou NE, Kay CM, et al. Packing and hydrophobicity effects on protein folding and stability: effects of beta-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers. Protein Sci. 1993;2(3):383-94.
Zhu, B. Y., Zhou, N. E., Kay, C. M., & Hodges, R. S. (1993). Packing and hydrophobicity effects on protein folding and stability: effects of beta-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers. Protein Science : a Publication of the Protein Society, 2(3), 383-94.
Zhu BY, et al. Packing and Hydrophobicity Effects On Protein Folding and Stability: Effects of Beta-branched Amino Acids, Valine and Isoleucine, On the Formation and Stability of Two-stranded Alpha-helical Coiled Coils/leucine Zippers. Protein Sci. 1993;2(3):383-94. PubMed PMID: 8453376.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Packing and hydrophobicity effects on protein folding and stability: effects of beta-branched amino acids, valine and isoleucine, on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers. AU - Zhu,B Y, AU - Zhou,N E, AU - Kay,C M, AU - Hodges,R S, PY - 1993/3/1/pubmed PY - 1993/3/1/medline PY - 1993/3/1/entrez SP - 383 EP - 94 JF - Protein science : a publication of the Protein Society JO - Protein Sci VL - 2 IS - 3 N2 - The aim of this study was to examine the differences between hydrophobicity and packing effects in specifying the three-dimensional structure and stability of proteins when mutating hydrophobes in the hydrophobic core. In DNA-binding proteins (leucine zippers), Leu residues are conserved at positions "d," and beta-branched amino acids, Ile and Val, often occur at positions "a" in the hydrophobic core. In order to discern what effect this selective distribution of hydrophobes has on the formation and stability of two-stranded alpha-helical coiled coils/leucine zippers, three Val or three Ile residues were simultaneously substituted for Leu at either positions "a" (9, 16, and 23) or "d" (12, 19, and 26) in both chains of a model coiled coil. The stability of the resulting coiled coils was monitored by CD in the presence of Gdn.HCl. The results of the mutations of Ile to Val at either positions "a" or "d" in the reduced or oxidized coiled coils showed a significant hydrophobic effect with the additional methylene group in Ile stabilizing the coiled coil (delta delta G values range from 0.45 to 0.88 kcal/mol/mutation). The results of mutations of Leu to Ile or Val at positions "a" in the reduced or oxidized coiled coils showed a significant packing effect in stabilizing the coiled coil (delta delta G values range from 0.59 to 1.03 kcal/mol/mutation). Our results also indicate the subtle control hydrophobic packing can have not only on protein stability but on the conformation adopted by the amphipathic alpha-helices. These structural findings correlate with the observation that in DNA-binding proteins, the conserved Leu residues at positions "d" are generally less tolerant of amino acid substitutions than the hydrophobic residues at positions "a." SN - 0961-8368 UR - https://www.unboundmedicine.com/medline/citation/8453376/Packing_and_hydrophobicity_effects_on_protein_folding_and_stability:_effects_of_beta_branched_amino_acids_valine_and_isoleucine_on_the_formation_and_stability_of_two_stranded_alpha_helical_coiled_coils/leucine_zippers_ L2 - https://doi.org/10.1002/pro.5560020310 DB - PRIME DP - Unbound Medicine ER -