G-protein-coupled receptors (GPCRs) form the largest class of membrane proteins and are an important target for therapeutic drugs. These receptors are highly dynamic proteins sampling a range of conformational states in order to fulfil their complex signalling roles. In order to fully understand GPCR signalling mechanisms it is necessary to extract the receptor protein out of the plasma membrane. Historically this has universally required detergents which inadvertently strip away the annulus of lipid in close association with the receptor and disrupt lateral pressure exerted by the bilayer. Detergent-solubilized GPCRs are very unstable which presents a serious hurdle to characterization by biophysical methods. A range of strategies have been developed to ameliorate the detrimental effect of removing the receptor from the membrane including amphipols and reconstitution into nanodics stabilized by membrane scaffolding proteins (MSPs) but they all require exposure to detergent. Poly(styrene-co-maleic acid) (SMA) incorporates into membranes and spontaneously forms nanoscale poly(styrene-co-maleic acid) lipid particles (SMALPs), effectively acting like a ‘molecular pastry cutter’ to ‘solubilize’ GPCRs in the complete absence of detergent at any stage and with preservation of the native annular lipid throughout the process. GPCR–SMALPs have similar pharmacological properties to membrane-bound receptor, exhibit enhanced stability compared with detergent-solubilized receptors and being non-proteinaceous in nature, are fully compatible with downstream biophysical analysis of the encapsulated GPCR.
Skip Nav Destination
Article navigation
April 2016
-
Cover Image
Cover Image
Endoplasmic reticulumendosome contact sites. This pseudo-colored electron microscopy image shows the formation of inter-organelle membrane contact sites between late endosomes (magenta) and the endoplasmic reticulum (ER; green). This tethering results from the interaction between two ER-anchored proteins (VAP-A and VAP-B) and the late endosomeanchored protein STARD3NL. Mitochondria: brown; nucleus: blue. For further details see pp. 493-498. Image kindly provided by Fabien Alpy. - PDF Icon PDF LinkTable of Contents
Review Article|
April 11 2016
GPCR–styrene maleic acid lipid particles (GPCR–SMALPs): their nature and potential
Mark Wheatley;
Mark Wheatley
2
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
2To whom correspondence should be addressed (email m.wheatley@bham.ac.uk).
Search for other works by this author on:
Jack Charlton;
Jack Charlton
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
Mohammed Jamshad;
Mohammed Jamshad
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
Sarah J. Routledge;
Sarah J. Routledge
1
†School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
Search for other works by this author on:
Sian Bailey;
Sian Bailey
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
Penelope J. La-Borde;
Penelope J. La-Borde
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
Maria T. Azam;
Maria T. Azam
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
Richard T. Logan;
Richard T. Logan
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
Roslyn M. Bill;
Roslyn M. Bill
†School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
Search for other works by this author on:
Tim R. Dafforn;
Tim R. Dafforn
*School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
Search for other works by this author on:
David R. Poyner
David R. Poyner
†School of Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K.
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
February 12 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (2): 619–623.
Article history
Received:
February 12 2016
Citation
Mark Wheatley, Jack Charlton, Mohammed Jamshad, Sarah J. Routledge, Sian Bailey, Penelope J. La-Borde, Maria T. Azam, Richard T. Logan, Roslyn M. Bill, Tim R. Dafforn, David R. Poyner; GPCR–styrene maleic acid lipid particles (GPCR–SMALPs): their nature and potential. Biochem Soc Trans 15 April 2016; 44 (2): 619–623. doi: https://doi.org/10.1042/BST20150284
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.