Journal article
Contribution of Hydrophobic Interactions to Protein Stability
Journal of molecular biology, Vol.408(3), pp.514-528
2011
DOI: 10.1016/j.jmb.2011.02.053
PMCID: PMC3086625
PMID: 21377472
Abstract
Our goal was to gain a better understanding of the contribution of hydrophobic interactions to protein stability. We measured the change in conformational stability, Δ(Δ
G), for hydrophobic mutants of four proteins: villin headpiece subdomain (VHP) with 36 residues, a surface protein from
Borrelia burgdorferi (VlsE) with 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa and T1. We compared our results with those of previous studies and reached the following conclusions: (1) Hydrophobic interactions contribute less to the stability of a small protein, VHP (0.6
±
0.3 kcal/mol per –CH
2– group), than to the stability of a large protein, VlsE (1.6
±
0.3 kcal/mol per –CH
2– group). (2) Hydrophobic interactions make the major contribution to the stability of VHP (40 kcal/mol) and the major contributors are (in kilocalories per mole) Phe18 (3.9), Met13 (3.1), Phe7 (2.9), Phe11 (2.7), and Leu21 (2.7). (3) Based on the Δ(Δ
G) values for 148 hydrophobic mutants in 13 proteins, burying a –CH
2– group on folding contributes, on average, 1.1
±
0.5 kcal/mol to protein stability. (4) The experimental Δ(Δ
G) values for aliphatic side chains (Ala, Val, Ile, and Leu) are in good agreement with their Δ
G
tr values from water to cyclohexane. (5) For 22 proteins with 36 to 534 residues, hydrophobic interactions contribute 60
±
4% and hydrogen bonds contribute 40
±
4% to protein stability. (6) Conformational entropy contributes about 2.4 kcal/mol per residue to protein instability. The globular conformation of proteins is stabilized predominantly by hydrophobic interactions.
Details
- Title: Subtitle
- Contribution of Hydrophobic Interactions to Protein Stability
- Creators
- C. Nick Pace - Texas A&M UniversityHailong Fu - Texas A&M UniversityKatrina Lee Fryar - Texas A&M Health Science CenterJohn Landua - Texas A&M Health Science CenterSaul R. Trevino - Texas A&M Health Science CenterBret A. Shirley - Texas A&M UniversityMarsha McNutt Hendricks - Texas A&M UniversitySatoshi Iimura - Texas A&M Health Science CenterKetan Gajiwala - Texas A&M UniversityJ. Martin Scholtz - Texas A&M UniversityGerald R. Grimsley - Texas A&M Health Science Center
- Resource Type
- Journal article
- Publication Details
- Journal of molecular biology, Vol.408(3), pp.514-528
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.jmb.2011.02.053
- PMID
- 21377472
- PMCID
- PMC3086625
- ISSN
- 0022-2836
- eISSN
- 1089-8638
- Language
- English
- Date published
- 2011
- Academic Unit
- Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Chemistry
- Record Identifier
- 9984293084202771
Metrics
28 Record Views