PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore

Chowdhury, Ranjana; Ren, Tingwei; Shankla, Manish; Decker, Karl; Grisewood, Matthew J.; Prabhakar, Jeevan; Baker, Carol S.; Golbeck, John H.; Aksimentiev, Aleksei; Kumar, Manish; Maranas, Costas D.

doi:10.1038/s41467-018-06097-1

Cited by 55 publications

(54 citation statements)

References 70 publications

(95 reference statements)

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“…A remaining challenge is to create tools for membrane proteins (3): a class of molecules that constitute over 30% of all proteins (4) and are targets for 60% of pharmaceuticals (5). There have been several achievements in membrane protein design including a zinc-transporting tetramer Rocker (6), an ion-conducting protein based on the Escherichia Coli Wza transporter (7), β-barrel pores with increased selectivity (8), receptors with new ligand-binding properties (9,10), and designed de novo α-helical bundles that insert into the membrane (11). For these advances, design of lipid-facing positions often used a native sequence or restricted the chemistry and/or size of amino acids.…”

mentioning

confidence: 99%

Protein structure prediction and design in a biologically-realistic implicit membrane

Alford

Fleming

et al. 2019

Preprint

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Protein design is a powerful tool for elucidating mechanisms of function and engineering new therapeutics and nanotechnologies. While soluble protein design has advanced, membrane protein design remains challenging due to difficulties in modeling the lipid bilayer. In this work, we developed an implicit approach that captures the anisotropic structure, shape of water-filled pores, and nanoscale dimensions of membranes with different lipid compositions. The model improves performance in computational benchmarks against experimental targets including prediction of protein orientations in the bilayer, ∆∆G calculations, native structure discrimination, and native sequence recovery. When applied to de novo protein design, this approach designs sequences with an amino acid distribution near the native amino acid distribution in membrane proteins, overcoming a critical flaw in previous membrane models that were prone to generating leucine-rich designs. Further, the proteins designed in the new membrane model exhibit native-like features including interfacial aromatic side chains, hydrophobic lengths compatible with bilayer thickness, and polar pores. Our method advances high-resolution membrane protein structure prediction and design toward tackling key biological questions and engineering challenges.membrane proteins | lipid composition | energy function | structure prediction | protein design

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confidence: 99%

Protein structure prediction and design in a biologically-realistic implicit membrane

Alford

Fleming

et al. 2019

Preprint

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“…Hence, it may be possible to increase periplasmic HM concentrations by overexpressing divalent cation-selective porins to improve the overall uptake rate from the periplasm into the cytoplasm for storage. It may also be possible to engineer porins with altered HM selectivity using the PoreDesigner workflow (Chowdhury et al, 2018 ).…”

Section: Strategies and Limitationsmentioning

confidence: 99%

Heavy Metal Removal by Bioaccumulation Using Genetically Engineered Microorganisms

Diep

Mahadevan

Yakunin

2018

Front. Bioeng. Biotechnol.

242

100

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Wastewater effluents from mines and metal refineries are often contaminated with heavy metal ions, so they pose hazards to human and environmental health. Conventional technologies to remove heavy metal ions are well-established, but the most popular methods have drawbacks: chemical precipitation generates sludge waste, and activated carbon and ion exchange resins are made from unsustainable non-renewable resources. Using microbial biomass as the platform for heavy metal ion removal is an alternative method. Specifically, bioaccumulation is a natural biological phenomenon where microorganisms use proteins to uptake and sequester metal ions in the intracellular space to utilize in cellular processes (e.g., enzyme catalysis, signaling, stabilizing charges on biomolecules). Recombinant expression of these import-storage systems in genetically engineered microorganisms allows for enhanced uptake and sequestration of heavy metal ions. This has been studied for over two decades for bioremediative applications, but successful translation to industrial-scale processes is virtually non-existent. Meanwhile, demands for metal resources are increasing while discovery rates to supply primary grade ores are not. This review re-thinks how bioaccumulation can be used and proposes that it can be developed for bioextractive applications—the removal and recovery of heavy metal ions for downstream purification and refining, rather than disposal. This review consolidates previously tested import-storage systems into a biochemical framework and highlights efforts to overcome obstacles that limit industrial feasibility, thereby identifying gaps in knowledge and potential avenues of research in bioaccumulation.

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“…These proteins have six membrane spanning domains that are composed of alpha helices and they form an hourglass structure that provides transport of water [63][64][65]. The structure and functions of aquaporins have been studied extensively in the last two decades [63,64,[66][67][68][69][70][71][72][73][74][75][76][77][78][79][80]. More than 450 homologs of aquaporins are found in bacterial and mammalian cells [81].…”

Section: Water Transport Across Cell Membranesmentioning

confidence: 99%

Biomimetic and bioinspired membranes for water purification: A critical review and future directions

Wagh

Escobar

2019

Env Prog and Sustain Energy

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Various types of channel proteins, broadly named porins, present in the cell membrane of gram‐negative bacteria have specific functionalities depending on their selectivity toward different nutrients or toward water. The high selectivity of porins has led to their incorporation into synthetic systems, in a field called biomimetics. An example is the addition of water channel proteins, or aquaporins, to polymeric separations membranes in order to enhance their performance in terms of selectivity and permeability. The concept of incorporating aquaporins into synthetic membranes has been studied for the last 10 years; however, there are still limitations such as costs, alignment into the membrane assembly, and scalability of membrane fabrication. Therefore, in recent years, there has been an increase in the study of synthesizing molecules with similar structure–function relationships of porins. These artificial channels attempt to mimic the biological porins, while being synthesized using simpler chemistry, being solvent compatible, and requiring less space on the membrane surface which helps to incorporate more channels into the membrane assembly. In summary, the future of biomimetic and bioinspired membranes depends on the design strategies, level of nature imitation, and the performance of these systems on a commercial scale. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13215, 2019

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PoreDesigner for tuning solute selectivity in a robust and highly permeable outer membrane pore

Cited by 55 publications

References 70 publications

Protein structure prediction and design in a biologically-realistic implicit membrane

Protein structure prediction and design in a biologically-realistic implicit membrane

Heavy Metal Removal by Bioaccumulation Using Genetically Engineered Microorganisms

Biomimetic and bioinspired membranes for water purification: A critical review and future directions

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