DOI: 10.1073/pnas.1614609114
论文题名: Trimethylamine N-oxide stabilizes proteins via a distinct mechanism compared with betaine and glycine
作者: Liao Y.-T. ; Manson A.C. ; DeLyser M.R. ; Noid W.G. ; Cremer P.S.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2017
卷: 114, 期: 10 起始页码: 2479
结束页码: 2484
语种: 英语
英文关键词: MD simulations
; Mechanism
; Osmolytes
; Protein folding
; Spectroscopy
Scopus关键词: betaine
; elastin like polypeptide
; glycine
; polymer
; polypeptide
; trimethylamine oxide
; unclassified drug
; water
; betaine
; elastin
; glycine
; methylamine
; peptide
; trimethyloxamine
; Article
; hydrophobicity
; molecular dynamics
; priority journal
; protein conformation
; protein folding
; protein stability
; proton transport
; solvation
; surface tension
; water structure
; air
; analysis
; chemical phenomena
; chemistry
; osmotic pressure
; solution and solubility
; Air
; Betaine
; Elastin
; Glycine
; Hydrophobic and Hydrophilic Interactions
; Methylamines
; Molecular Dynamics Simulation
; Osmotic Pressure
; Peptides
; Protein Folding
; Solutions
; Surface Tension
; Water
英文摘要: We report experimental and computational studies investigating the effects of three osmolytes, trimethylamine N-oxide (TMAO), betaine, and glycine, on the hydrophobic collapse of an elastin-like polypeptide (ELP). All three osmolytes stabilize collapsed conformations of the ELP and reduce the lower critical solution temperature (LSCT) linearly with osmolyte concentration. As expected from conventional preferential solvation arguments, betaine and glycine both increase the surface tension at the air-water interface. TMAO, however, reduces the surface tension. Atomically detailed molecular dynamics (MD) simulations suggest that TMAO also slightly accumulates at the polymer-water interface, whereas glycine and betaine are strongly depleted. To investigate alternative mechanisms for osmolyte effects, we performed FTIR experiments that characterized the impact of each cosolvent on the bulk water structure. These experiments showed that TMAO red-shifts the OH stretch of the IR spectrum via a mechanism that was very sensitive to the protonation state of the NO moiety. Glycine also caused a red shift in the OH stretch region, whereas betaine minimally impacted this region. Thus, the effects of osmolytes on the OH spectrum appear uncorrelated with their effects upon hydrophobic collapse. Similarly, MD simulations suggested that TMAO disrupts the water structure to the least extent, whereas glycine exerts the greatest influence on the water structure. These results suggest that TMAO stabilizes collapsed conformations via a mechanism that is distinct from glycine and betaine. In particular, we propose that TMAO stabilizes proteins by acting as a surfactant for the heterogeneous surfaces of folded proteins. © 2017, National Academy of Sciences. All rights reserved. Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163867
Appears in Collections: 气候变化与战略
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作者单位: Liao, Y.-T., Department of Chemistry, Penn State University, University Park, PA 16802, United States; Manson, A.C., Department of Chemistry, Penn State University, University Park, PA 16802, United States; DeLyser, M.R., Department of Chemistry, Penn State University, University Park, PA 16802, United States; Noid, W.G., Department of Chemistry, Penn State University, University Park, PA 16802, United States; Cremer, P.S., Department of Chemistry, Penn State University, University Park, PA 16802, United States, Department of Biochemistry and Molecular Biology, Penn State University, University Park, PA 16802, United States
Recommended Citation:
Liao Y.-T.,Manson A.C.,DeLyser M.R.,et al. Trimethylamine N-oxide stabilizes proteins via a distinct mechanism compared with betaine and glycine[J]. Proceedings of the National Academy of Sciences of the United States of America,2017-01-01,114(10)