scholarly journals Development and Application of Non-Additive Force Fields for Molecular Simulations of Lipid Bilayers and Integral Membrane Proteins

2010 ◽  
Vol 98 (3) ◽  
pp. 575a
Author(s):  
Sandeep Patel
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Force Fields ◽  
Molecular Simulations ◽  
Integral Membrane Proteins

scholarly journals Lipid Transporters Beam Signals from Cell Membranes

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 562
Author(s):  
Miliça Ristovski ◽  
Danny Farhat ◽  
Shelly Ellaine M. Bancud ◽  
Jyh-Yeuan Lee
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Lipid Composition ◽  
Structural Integrity ◽  
Current Knowledge ◽  
Integral Membrane Proteins ◽  
Cellular Membranes ◽  
Cytoplasmic Proteins ◽  
Lipid Transporters

Lipid composition in cellular membranes plays an important role in maintaining the structural integrity of cells and in regulating cellular signaling that controls functions of both membrane-anchored and cytoplasmic proteins. ATP-dependent ABC and P4-ATPase lipid transporters, two integral membrane proteins, are known to contribute to lipid translocation across the lipid bilayers on the cellular membranes. In this review, we will highlight current knowledge about the role of cholesterol and phospholipids of cellular membranes in regulating cell signaling and how lipid transporters participate this process.

scholarly journals CellectSeq: In silico discovery of antibodies targeting integral membrane proteins combining in situ selections and next-generation sequencing

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Abdellali Kelil ◽  
Eugenio Gallo ◽  
Sunandan Banerjee ◽  
Jarrett J. Adams ◽  
Sachdev S. Sidhu
Keyword(s):  
Next Generation Sequencing ◽  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Cost Effective ◽  
Integral Membrane Proteins ◽  
Sequencing Error ◽  
Next Generation ◽  
Synthetic Antibody ◽  
Generation Sequencing

AbstractSynthetic antibody (Ab) technologies are efficient and cost-effective platforms for the generation of monoclonal Abs against human antigens. Yet, they typically depend on purified proteins, which exclude integral membrane proteins that require the lipid bilayers to support their native structure and function. Here, we present an Ab discovery strategy, termed CellectSeq, for targeting integral membrane proteins on native cells in complex environment. As proof of concept, we targeted three transmembrane proteins linked to cancer, tetraspanin CD151, carbonic anhydrase 9, and integrin-α11. First, we performed in situ cell-based selections to enrich phage-displayed synthetic Ab pools for antigen-specific binders. Then, we designed next-generation sequencing procedures to explore Ab diversities and abundances. Finally, we developed motif-based scoring and sequencing error-filtering algorithms for the comprehensive interrogation of next-generation sequencing pools to identify Abs with high diversities and specificities, even at extremely low abundances, which are very difficult to identify using manual sampling or sequence abundances.

The effect of hydrodynamic interactions on the tracer and gradient diffusion of integral membrane proteins in lipid bilayers

1994 ◽  
Vol 258 ◽  
pp. 167-190 ◽  
Author(s):  
Stuart J. Bussell ◽  
Daniel A. Hammer ◽  
Donald L. Koch
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Stokes Equations ◽  
Thin Sheet ◽  
Three Dimensional ◽  
Integral Membrane Proteins ◽  
Area Fraction ◽  
Hydrodynamic Interactions ◽  
Low Viscosity ◽  
Long Time

Biological membranes can be considered two-dimensional fluids with suspended integral membrane proteins (IMPs). We have calculated the effect of hydrodynamic interactions on the various diffusion coefficients of IMPs in lipid bilayers. The IMPs are modelled as hard cylinders of radius a immersed in a thin sheet of viscosity μ and thickness h bounded by a fluid of low viscosity μ′. We have ensemble averaged the N-body Stokes equations to the pair level and have renormalized them following the methods of Batchelor (1972) and Hinch (1977). The lengthscale for the hydrodynamic interactions is λa = μh / μ′, Which is O (100a), and the slow decay of the interactions introduces new features in the renormalizations compared to the analogous analyses for three-dimensional suspensions of spheres.We have calculated the asymptotic limits for the short- and long-time tracer diffusivities, Ds and Dl, respectively, and for the gradient diffusivity, Dg, for ϕ [Lt ] 1 and λ [Gt ] 1, where ϕ is the IMP area fraction and λ = μh / (μ′a). The diffusivities are \begin{eqnarray*} D_s/D_0 &=& 1-2\phi[1-(1+\ln (2)-9/32)/(\ln(\lambda)-\gamma)], D_l/D_0 &=& D_s/D_0 - 0.07/(\ln(\lambda)-\gamma), D_g/D_0 &=& 1+\phi[-7+(6\ln(2)+7/16+0.37)/(\ln(\lambda)-\gamma)], \end{eqnarray*} where D0 is the diffusivity in the limit of zero area fraction, and γ = 0.577216 is Euler's constant. The results for Dl and Ds differ only slightly. The decrease in Dg/Do as ϕ increases contrasts with the result for spheres for which Dg/Do > 1.

scholarly journals CellectSeq: In Silico Discovery of Antibodies Targeting Integral Membrane Proteins Combining In Situ Selections of Phage Displayed Synthetic Antibodies and Next-Generation Sequencing

2020 ◽  
Author(s):  
Abdellali Kelil ◽  
Eugenio Gallo ◽  
Jarrett Adams ◽  
Jason Moffat ◽  
Sachdev Sidhu
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayers ◽  
Cost Effective ◽  
Integral Membrane Proteins ◽  
Native Form ◽  
Surface Receptors ◽  
Synthetic Antibody ◽  
Ngs Data ◽  
Generation Sequencing

Abstract Synthetic antibody (Ab) technologies are efficient and cost-effective platforms for the generation of monoclonal proteomic tools against human antigens. Yet, they typically depend on purified proteins, which exclude from interrogation integral membrane proteins that require the lipid bilayers to support their native form or function. Here, we present a novel Ab discovery strategy, termed CellectSeq, for targeting integral membrane proteins presented on native cells in complex environment. As proof of concept, we targeted the challenging tetraspanin receptor CD151, a target linked to cancer. First, we optimized in situ cell-based selections to enrich Ab pools for antigen-specific binders. Then, we designed novel NGS procedures to explore Ab pools diversities and abundances with enhanced accuracies. Finally, we developed novel motif-based scoring and error filtering algorithms for the comprehensive interrogation of NGS data to identify Abs with high diversities and specificities, even at extremely low abundances. We identified highly selective and diversified Abs against CD151 with abundance as low as 0.00009% for which manual sampling or identification using Abs abundances in NGS data would have been impossible. Here we show that CellectSeq enables the rapid discovery of diversified and selective antibodies against CD151, with implications for other integral membrane proteins and cell-surface receptors.

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