The role of electrostatics in protein–membrane interactions

Mulgrew-Nesbitt, Anna; Diraviyam, Karthikeyan; Wang, Jiyao; Singh, Shaneen; Murray, Paul; Li, Zhaohui; Rogers, Laura; Mirkovic, Nebojsa; Murray, Diana

doi:10.1016/j.bbalip.2006.07.002

Cited by 174 publications

(181 citation statements)

References 120 publications

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“…This reversible order (half-barrel) 7 disorder 7 order (helix) transition driven by the redox state of the flavin cofactor appears to be a unique regulation mechanism for peripheral membrane association. In many peripheral membrane proteins studied, membrane association/dissociation involves a change of the net charge of basic membrane binding patches by phosphorylation/dephosphorylation (protein kinase C) or charge neutralization by calcium binding (C2 domains of phospholipase A2 and 5-lipoxygenase) (41). There are also instances where basic patches are occluded becoming uncovered upon binding/dissociation of effectors (Gß␥/G␣ complex) (41).…”

Section: Discussionmentioning

confidence: 99%

“…In many peripheral membrane proteins studied, membrane association/dissociation involves a change of the net charge of basic membrane binding patches by phosphorylation/dephosphorylation (protein kinase C) or charge neutralization by calcium binding (C2 domains of phospholipase A2 and 5-lipoxygenase) (41). There are also instances where basic patches are occluded becoming uncovered upon binding/dissociation of effectors (Gß␥/G␣ complex) (41). Although all basic residues (R 552 , R 558 , K 567 , R 572 ) of the AP are exposed to the solvent, full-length EcPOX in the oxidized state does not bind to membranes (see Fig.…”

Section: Discussionmentioning

confidence: 99%

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Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli

Neumann

Weidner

Pech

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The thiamin-and flavin-dependent peripheral membrane enzyme pyruvate oxidase from E. coli catalyzes the oxidative decarboxylation of the central metabolite pyruvate to CO2 and acetate. Concomitant reduction of the enzyme-bound flavin triggers membrane binding of the C terminus and shuttling of 2 electrons to ubiquinone 8, a membrane-bound mobile carrier of the electron transport chain. Binding to the membrane in vivo or limited proteolysis in vitro stimulate the catalytic proficiency by 2 orders of magnitude. The molecular mechanisms by which membrane binding and activation are governed have remained enigmatic. Here, we present the X-ray crystal structures of the full-length enzyme and a proteolytically activated truncation variant lacking the last 23 C-terminal residues inferred as important in membrane binding. In conjunction with spectroscopic results, the structural data pinpoint a conformational rearrangement upon activation that exposes the autoinhibitory C terminus, thereby freeing the active site. In the activated enzyme, Phe-465 swings into the active site and wires both cofactors for efficient electron transfer. The isolated C terminus, which has no intrinsic helix propensity, folds into a helical structure in the presence of micelles.electron transfer ͉ membrane protein ͉ X-ray crystallography R eversible binding of peripheral membrane proteins to the lipid bilayer regulates cell signaling, lipid metabolism and many other cellular events. Proteins that adhere directly to the biological membrane are termed amphitropic proteins and can attach to the bilayer through interaction of amphipathic helices, hydrophobic loops, ions, or covalently attached lipids (1, 2). In many cases studied, these proteins exhibit a very low basal membrane affinity, becoming recruited to the membrane from the cytosol only after a conformational transition or electrostatic switch that not only triggers membrane binding but may also initiate or elevate biological activity (3). Despite many recent advances in understanding how membrane binding and concomitant functional activation of proteins are regulated, there remains a paucity of structural data that allow detailed atomic insights into the nature of reversible protein-membrane interaction and of structural transitions that trigger membrane binding and functionality.In this regard, the thiamin diphosphate-(ThDP, the functional derivative of vitamin B1) and flavin-dependent pyruvate oxidase from Escherichia coli (EcPOX, EC 1.2.2.2) is a particularly interesting and extensively studied peripheral membrane protein that feeds electrons from the cytosol directly into the respiratory chain at the membrane (4-11). EcPOX supports aerobic growth in E. coli as a backup system to the pyruvate dehydrogenase multienzyme complex and catalyzes the oxidative decarboxylation of the metabolite pyruvate to carbon dioxide and acetate (12). The 2 electrons arising from oxidation of pyruvate at the ThDP site are transferred initially to the neighboring flavin (Eq.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli

Neumann

Weidner

Pech

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, there are a number of cases where a disease is attributable to the abrogation of these properties (22) (23). Bioinformatics and computational biology have also begun to play a major role in lipid-binding domain studies, eliciting predictions of potential lipid-binding proteins (24), the role of electrostatics in lipid binding (25), and assembly of databases that compile lipid-binding domain data and predictions of membrane binding properties (26,27). The BAR domain field is one area where atomistic molecular dynamics simulations have excelled.…”

Section: : S299-s304mentioning

confidence: 99%

Lipid binding domains: more than simple lipid effectors

Stahelin

2009

Journal of Lipid Research

124

105

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The spatial and temporal regulation of lipid molecules in cell membranes is a hallmark of cellular signaling and membrane trafficking events. Lipid-mediated targeting provides for strict control and versatility, because cell membranes harbor a large number of lipid molecules with variation in head group and acyl chain structures. Signaling and trafficking proteins contain a large number of modular domains that exhibit specific lipid binding properties and play a critical role in their localization and function. Nearly 20 years of research including structural, computational, biochemical and biophysical studies have demonstrated how these lipid-binding domains recognize their target lipid and achieve subcellular localization. The integration of this individual lipid-binding domain data in the context of the fulllength proteins, macromolecular signaling complexes, and the lipidome is only beginning to be unraveled and represents a target of therapeutic development. This review brings together recent findings and classical concepts to concisely summarize the lipid-binding domain field while illustrating where the field is headed and how the gaps may be filled in with new technologies.-Stahelin, R. V. Lipid binding domains: more than simple lipid effectors. J. Lipid Res. 2009. 50: S299-S304.

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“…The electrostatic phenomena occurring at the surface of lipid bilayers involve many factors and sre not fully understood [36]. The data obtained from the measurements of the f-potential gives an indication of average surface charge; however, it is not valid for the description of short range electrostatic interaction, as is the case of the viral particles adsorbing to the AEXc matrix, due to the complexity of the intervening factors [36,37].…”

Section: Characterization Of Intact and Envelope Protein-free Vectorsmentioning

confidence: 99%

“…Hence the lower binding strength of the Env -vectors to the AEXc matrix at the working pH of 7.5. It is also possible that the lipid bilayer of the viral particle increases the strength of adsorption of the Env + vectors to the AEXc matrix by locally affecting the electrostatic properties of the envelope proteins at pH values higher than the pI of Env -vectors [37]. These effects are not observed in nonenveloped viral particles (e. g., adenoviruses and rAAV), where the protein capsids adsorbed to the chromatographic matrix are displaced by NaCl concentrations lower than 600 mM [38], compared with 600 -1000 mM NaCl required for RVs.…”

Section: Characterization Of Intact and Envelope Protein-free Vectorsmentioning

confidence: 99%

Removal of envelope protein‐free retroviral vectors by anion‐exchange chromatography to improve product quality

Rodrigues

Alves

Lopes

et al. 2008

J of Separation Science

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Original PaperRemoval of envelope protein-free retroviral vectors by anion-exchange chromatography to improve product qualityWe have investigated the role of the retroviral lipid bilayer and envelope proteins in the adsorption of retroviral vectors (RVs) to a Fractogel TM DEAE matrix. Intact RVs and their degradation components (envelope protein-free vectors and solubilized vector components) were adsorbed to this matrix and eluted using a linear gradient. Envelope protein-free RVs (Env -) and soluble envelope proteins (gp70) eluted in a significantly lower range of conductivities than intact RVs (Env + ) (13.7 -30 mS/cm for Env -and gp70 proteins vs. 47 -80 mS/cm for Env + ). The zeta (f)-potential of Env + and Env -vectors was evaluated showing that envelope proteins define the pI of the viral particles (pI (Env + ) a 2 versus 3 a pI (Env -) a 4) and that Env + and Env -vectors have similar f-potentials within pH 5 and 8. The results presented herein indicate that the adsorption of retroviral particles occurs through multi-point interaction of the envelope proteins with the cationic groups on the chromatographic matrix. The strength of this adsorption is thus dependent on the amount of envelope protein present in the viral lipid bilayer. In conclusion, AEXc enables the separation of gp70 proteins as well as envelope protein-free vectors constituting a significant improvement to the quality of retroviral preparations for gene therapy applications.

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The role of electrostatics in protein–membrane interactions

Cited by 174 publications

References 120 publications

Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli

Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli

Lipid binding domains: more than simple lipid effectors

Removal of envelope protein‐free retroviral vectors by anion‐exchange chromatography to improve product quality

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