Overcoming bottlenecks in the membrane protein structural biology pipeline

Hardy, David, Bill, Roslyn M., Jawhari, Anass and Rothnie, Alice J. (2016). Overcoming bottlenecks in the membrane protein structural biology pipeline. Biochemical Society Transactions, 44 (3), pp. 838-844.

Abstract

Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future.

Publication DOI: https://doi.org/10.1042/BST20160049
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society. Biochemical Society Transactions. This is not the final peer-reviewed Version of Record. Funding: BBSRC Industrial CASE studentship with Calixar [BB/L015846/1]
Uncontrolled Keywords: calixarenes,maltose neopentyl glycol (MNG),membrane,solubilization,structural biology,styrene maleic acid lipid particle (SMALP),Biochemistry
Full Text Link: http://www.bioc ... ontent/44/3/838
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-06-09
Authors: Hardy, David
Bill, Roslyn M. ( 0000-0003-1331-0852)
Jawhari, Anass
Rothnie, Alice J. ( 0000-0002-4259-7015)

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