Toward a molecular understanding of protein solubility: increased negative surface charge correlates with increased solubility

Ryan M Kramer; Varad R Shende; Nicole Motl; C Nick Pace; J Martin Scholtz

doi:10.1016/j.bpj.2012.01.060

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Toward a molecular understanding of protein solubility: increased negative surface charge correlates with increased solubility

Journal article

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Toward a molecular understanding of protein solubility: increased negative surface charge correlates with increased solubility

Ryan M Kramer, Varad R Shende, Nicole Motl, C Nick Pace and J Martin Scholtz

Biophysical journal, Vol.102(8), pp.1907-1915

04/18/2012

DOI: 10.1016/j.bpj.2012.01.060

PMCID: PMC3328702

PMID: 22768947

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Abstract

Protein solubility is a problem for many protein chemists, including structural biologists and developers of protein pharmaceuticals. Knowledge about how intrinsic factors influence solubility is limited due to the difficulty of obtaining quantitative solubility measurements. Solubility measurements in buffer alone are difficult to reproduce, because gels or supersaturated solutions often form, making it impossible to determine solubility values for many proteins. Protein precipitants can be used to obtain comparative solubility measurements and, in some cases, estimations of solubility in buffer alone. Protein precipitants fall into three broad classes: salts, long-chain polymers, and organic solvents. Here, we compare the use of representatives from two classes of precipitants, ammonium sulfate and polyethylene glycol 8000, by measuring the solubility of seven proteins. We find that increased negative surface charge correlates strongly with increased protein solubility and may be due to strong binding of water by the acidic amino acids. We also find that the solubility results obtained for the two different precipitants agree closely with each other, suggesting that the two precipitants probe similar properties that are relevant to solubility in buffer alone.

Ammonium Sulfate - chemistry

Animals

Humans

Polyethylene Glycols - chemistry

Protein Stability

Proteins - chemistry

Solubility

Surface Properties

Details

Title: Subtitle: Toward a molecular understanding of protein solubility: increased negative surface charge correlates with increased solubility
Creators: Ryan M Kramer - Texas A&M University
Varad R Shende - University of Bremen
Nicole Motl - Texas A&M University
C Nick Pace - Texas A&M University
J Martin Scholtz - Texas A&M University
Resource Type: Journal article
Publication Details: Biophysical journal, Vol.102(8), pp.1907-1915
DOI: 10.1016/j.bpj.2012.01.060
PMID: 22768947
PMCID: PMC3328702
NLM abbreviation: Biophys J
ISSN: 0006-3495
eISSN: 1542-0086
Grant note: T32GM65088 / NIGMS NIH HHS T32 GM065088 / NIGMS NIH HHS
Language: English
Date published: 04/18/2012
Academic Unit: Research Administration; Pharmaceutical Sciences and Experimental Therapeutics; Biochemistry and Molecular Biology; Chemistry
Record Identifier: 9984293078902771

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