Folding and stability of integral membrane proteins in amphipols

Kleinschmidt, Jörg H.; Popot, Jean‐Luc

doi:10.1016/j.abb.2014.10.013

Cited by 48 publications

(35 citation statements)

References 164 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This complex phenomenon, which has been discussed elsewhere under the nickname of “Gulliver effect” (Kleinschmidt and Popot 2014;Picard et al 2006; Popot et al 2003, 2011) (Fig. 6) is thought to result from the activation free energy penalty for rearranging the backbone of the polymer to adapt to transconformations of the protein’s transmembrane surface.…”

Section: Basic Properties Of Amphipols and Membrane Protein/amphipol mentioning

confidence: 99%

“…Most MPs become more stable, generally much more so, when transferred from detergent to APols (reviewed in Kleinschmidt and Popot 2014; Popot 2010; Popot et al 2011) (Fig. 5).…”

Section: Basic Properties Of Amphipols and Membrane Protein/amphipol mentioning

confidence: 99%

“…Whereas it is recommended to handle MP/APol complexes in the presence of some excess of APol to keep them from forming oligomers (see “Composition and Organization” section), this excess can be very small (for tOmpA, typically one free particle per complex; see Zoonens et al 2007), which limits the volume of the hydrophobic sink into which lipids and subunits can disperse, a major cause of inactivation by detergent solutions (for a discussion, see Gohon and Popot 2003; Kleinschmidt and Popot 2014; Popot 2010). …”

Section: Basic Properties Of Amphipols and Membrane Protein/amphipol mentioning

confidence: 99%

“…Probably because they compete less efficiently than detergents with the protein/protein and protein/lipid interactions that determine and stabilize the 3D structure of MPs, APols have turned out to be a remarkably efficient medium in which to fold or refold MPs that have been obtained in denatured state, typically as the result of solubilizing inclusion bodies in either sodium dodecylsulfate (SDS, for α -helical MPs) or urea (for β -barrel ones) (reviewed by Kleinschmidt and Popot 2014). At the date of this writing, seven α -helical MPs, including six GPCRs, have been folded in vitro using APols, and four β -barrel ones (see Table 7), with typical yields ranging between 60 and >90 %.…”

Section: Applicationsmentioning

confidence: 99%

See 3 more Smart Citations

Amphipols for Each Season

2014

Self Cite

View full text Add to dashboard Cite

Amphipols (APols) are short amphipathic polymers that can substitute for detergents at the transmembrane surface of membrane proteins (MPs) and, thereby, keep them soluble in detergent-free aqueous solutions. APol-trapped MPs are, as a rule, more stable biochemically than their detergent-solubilized counterparts. APols have proven useful to produce MPs, most noticeably by assisting their folding from the denatured state obtained after solubilizing MP inclusion bodies in either SDS or urea. They facilitate the handling in aqueous solution of fragile MPs for the purpose of proteomics, structural and functional studies, and therapeutics. Because APols can be chemically labeled or functionalized, and they form very stable complexes with MPs, they can also be used to functionalize those indirectly, which opens onto many novel applications. Following a brief recall of the properties of APols and MP/APol complexes, an update is provided of recent progress in these various fields.

show abstract

Section: Basic Properties Of Amphipols and Membrane Protein/amphipol mentioning

confidence: 99%

“…Most MPs become more stable, generally much more so, when transferred from detergent to APols (reviewed in Kleinschmidt and Popot 2014; Popot 2010; Popot et al 2011) (Fig. 5).…”

Section: Basic Properties Of Amphipols and Membrane Protein/amphipol mentioning

confidence: 99%

Section: Basic Properties Of Amphipols and Membrane Protein/amphipol mentioning

confidence: 99%

Section: Applicationsmentioning

confidence: 99%

See 2 more Smart Citations

Amphipols for Each Season

2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…As a final perspective on MP protein folding, Jean-Luc Popot continues with Jörg Kleinschmidt in a description of a synthetic group of amphipathic polymers called amphipols (APols) which hold great promise both in folding and stabilizing membrane proteins [5]. Like detergents, they contain both hydrophilic groups and hydrophobic chains, but as (short) polymers they interact less invasively with MPs than detergents do.…”

mentioning

confidence: 98%

Membrane protein folding and stability

Otzen

2014

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

Recent Advances on Polymer Lipid Particles ( PoLP ) in Membrane Protein Research

Lousa

Postis

2018

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

Membrane proteins (MPs) structure elucidation is of crucial importance as they represent a major target for drug design. However, owing to their high hydrophobicity, MPs are challenging proteins to study. The use of polymer lipid nanoparticles (PoLP) has recently allowed a leap forward in the field of MP research. A wide range of polymers have been successfully used for elucidating the structure of MPs. One polymer in particular, styrene maleic acid (SMA) copolymer, is recently catching a large interest owing to its easy use in detergent‐free membrane solubilisation and the recent successes in purification and stabilising MPs for further biophysical studies. Key Concepts SMA copolymers are new tools to purify membrane proteins. SMA copolymers can solubilise membrane proteins directly without the need of detergents. Membrane proteins purified in SMALP are stable over time and remain active owing to the retention of native lipids around the proteins. SMA use limitations include acid pH sensitivity, divalent cations sensitivity and UV absorption. New polymers (SMA and others) are being engineered to overcome these limitations.

show abstract

Folding and stability of integral membrane proteins in amphipols

Cited by 48 publications

References 164 publications

Amphipols for Each Season

Amphipols for Each Season

Membrane protein folding and stability

Recent Advances on Polymer Lipid Particles ( PoLP ) in Membrane Protein Research

Contact Info

Product

Resources

About