Tripod amphiphiles for membrane protein manipulation

Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA. .
Molecular BioSystems (Impact Factor: 3.18). 12/2009; 6(1):89-94. DOI: 10.1039/b915162c
Source: PubMed

ABSTRACT Integral membrane proteins (IMPs) are crucial biological components, mediating the transfer of material and information between cells and their environment. Many IMPs have proven to be difficult to isolate and study. High-resolution structural information on this class of proteins is limited, largely because of difficulties in generating soluble forms of such proteins that retain native folding and activity, and difficulties in generating high-quality crystals from such preparations. Isolated IMPs typically do not dissolve in aqueous solution, a property that arises from the large patches of hydrophobic surface necessary for favorable interactions with the core of a lipid bilayer. Detergents are generally required for IMP solubilization: hydrophobic segments of detergent molecules cluster around and shield from water the hydrophobic protein surfaces. The critical role played by detergents in membrane protein manipulation, and the fact that many IMPs are recalcitrant to solubilization and/or crystallization with currently available detergents, suggest that it should be valuable to explore new types of amphiphiles for these purposes. This review constitutes a progress report on our long-term effort to develop a new class of organic molecules, collectively designated "tripod amphiphiles," that are intended as alternatives to conventional detergents for membrane protein manipulation. One long-range goal of this research is to identify new types of amphiphiles that facilitate IMP crystallization. This review should help introduce an important biochemical need to organic chemists, and perhaps inspire new approaches to the problem.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Detergents are widely used for membrane protein research; however, membrane proteins encapsulated in micelles formed by conventional detergents tend to undergo structural degradation, necessitating the development of new agents with enhanced efficacy. Here we prepared several hydrophobic variants of ganglio-tripod amphiphiles (TPAs) derived from previously reported TPAs and evaluated for a multi-subunit, pigment protein superassembly. In this study, TPA-16 was found to be most efficient in protein solubilization while TPA-15 proved most favourable in long-term protein stability. The current study combined with previous TPA studies enabled us to elaborate on a few detergent structure-property relationships that could provide useful guidelines for novel amphiphile design.
    Organic & Biomolecular Chemistry 08/2014; 12(42). DOI:10.1039/C4OB01375A · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We prepared adamantane-containing amphiphiles and evaluated with a large membrane protein complex in terms of protein solubilisation and stabilization efficacy. These agents were superior to conventional detergents, especially in terms of the membrane protein solubilisation efficiency, implying a new detergent structure-property relationship.
    Chemical Communications 08/2014; 50(82). DOI:10.1039/C4CC05746E · 6.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Membrane proteins (MPs) are insoluble in aqueous media as a result of incompatibility between the hydrophilic property of the solvent molecules and the hydrophobic nature of MP surfaces, normally associated with lipid membranes. Amphipathic compounds are necessary for extraction of these macromolecules from the native membranes and their maintenance in solution. The amphipathic agents surround the hydrophobic segments of MPs, thus serving as a membrane mimetic system. Of the available amphipathic agents, detergents are most widely used for MP manipulation. However, MPs encapsulated by conventional detergent micelles have a tendency to undergo structural degradation, hampering MP advance, and necessitating the development of novel detergents with enhanced efficacy for MP study. In this chapter, we will introduce both conventional and novel classes of detergents and discuss about the chemical structures, design principles, and efficacies of these compounds for MP solubilization and stabilization. The behaviors of those agents toward MP crystallization will be a primary topic in our discussion. This discussion highlights the common features of popular conventional/novel detergents essential for successful MP structural study. The conclusions reached by this discussion would not only enable MP scientists to rationally select a set of detergent candidates among a large number of detergents but also provide detergent inventors with useful guidelines in designing novel amphipathic systems. © 2015 Elsevier Inc. All rights reserved.
    Methods in enzymology 01/2015; 557:57-94. DOI:10.1016/bs.mie.2014.12.021 · 2.19 Impact Factor


Available from