Toward a Molecular Understanding of Protein Solubility: Increased Negative Surface Charge Correlates with Increased Solubility

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...

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Bibliographic Details
Published in:	Biophysical journal Vol. 102; no. 8; pp. 1907 - 1915
Main Authors:	Kramer, Ryan M., Shende, Varad R., Motl, Nicole, Pace, C. Nick, Scholtz, J. Martin
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 18-04-2012 Biophysical Society The Biophysical Society
Subjects:	Amino acids Ammonium Sulfate - chemistry Animals Binding sites Humans Mathematical models Molecular structure Polyethylene Glycols - chemistry Protein Protein Stability Proteins Proteins - chemistry Solubility Surface Properties
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0006-3495 1542-0086
DOI:	10.1016/j.bpj.2012.01.060