Oleksandr

Designed proteins induce the formation of nanocage-containing extracellular vesicles

Nature 540, 7632 (2016). doi:10.1038/nature20607

Authors: Jörg Votteler, Cassandra Ogohara, Sue Yi, Yang Hsia, Una Nattermann, David M. Belnap, Neil P. King & Wesley I. Sundquist

Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids or proteins, but strategies for engineering hybrid biological materials are only beginning to emerge. Here we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses. We refer to these hybrid biomaterials as ‘enveloped protein nanocages’ (EPNs). Robust EPN biogenesis requires protein sequence elements that encode three distinct functions: membrane binding, self-assembly, and recruitment of the endosomal sorting complexes required for transport (ESCRT) machinery. A variety of synthetic proteins with these functional elements induce EPN biogenesis, highlighting the modularity and generality of the design strategy. Biochemical analyses and cryo-electron microscopy reveal that one design, EPN-01, comprises small (~100 nm) vesicles containing multiple protein nanocages that closely match the structure of the designed 60-subunit self-assembling scaffold. EPNs that incorporate the vesicular stomatitis viral glycoprotein can fuse with target cells and deliver their contents, thereby transferring cargoes from one cell to another. These results show how proteins can be programmed to direct the formation of hybrid biological materials that perform complex tasks, and establish EPNs as a class of designed, modular, genetically-encoded nanomaterials that can transfer molecules between cells.

Abstract

Nature Chemistry. doi:10.1038/nchem.2675

Authors: Roy E. Schreiber, Lothar Houben, Sharon G. Wolf, Gregory Leitus, Zhong-Ling Lang, Jorge J. Carbó, Josep M. Poblet & Ronny Neumann

Homogeneous crystal nucleation has now been observed by transmission electron microscopy in real time on a molecular scale. Countercation-dependent observations of polyoxometalate proto-crystal formation confirm existence of a higher energy classical molecular attachment mechanism, as well as a lower energy two-step mechanism via an intermediate dense phase.

Nature Chemistry. doi:10.1038/nchem.2669

Authors: George Bepete, Eric Anglaret, Luca Ortolani, Vittorio Morandi, Kai Huang, Alain Pénicaud & Carlos Drummond

Aggregation usually prevents dissolution of graphene in water. Now, hydroxide ion adsorption has been shown to allow the stabilization of true single-layer graphene in water — with no surfactant required — so long as the liquid is degassed beforehand. The resulting aqueous dispersions can contain high concentrations of exfoliated graphene that are stable for several months.

Enzymes that catalyze carbon–silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon–hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon–silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules. Authors: S. B. Jennifer Kan, Russell D. Lewis, Kai Chen, Frances H. Arnold

Nature Chemistry. doi:10.1038/nchem.2664

Authors: Jianfeng Xu, Maria Tsanakopoulou, Christopher J. Magnani, Rafał Szabla, Judit E. Šponer, Jiří Šponer, Robert W. Góra & John D. Sutherland

Although ribose aminooxazoline has been shown to be a potential intermediate in prebiotic pyrimidine ribonucleotide synthesis, a route by which this could occur has remained elusive. Now, a remarkably efficient photoanomerization reaction has been investigated by theory and experiment. The new route affords enantiomerically pure ribonucleotides when the starting material is enantioenriched.

Non-directional yet specific: The van der Waals forces enable high-fidelity self-sorting of two homomeric hydrocarbon receptors for ligand-induced assembly of a ternary complex. The shape recognition exerted by the non-directional van der Waals forces allowed for specific repulsion of a diastereomeric receptor as the counterpart.

[Communication]
Taisuke Matsuno, Sota Sato, Atsutoshi Yokoyama, Sho Kamata, Hiroyuki Isobe
Angew. Chem. Int. Ed., November 16, 2016, DOI: 10.1002/anie.201609444. Read article

Abstract

Dr. Mohammadali Foroozandeh, Dr. Laura Castañar, Dr. Lucas G. Martins, Dr. Davy Sinnaeve, Guilherme Dal Poggetto, Prof. Claudio F. Tormena, Dr. Ralph W. Adams, Prof. Gareth A. Morris and Dr. Mathias Nilsson

Disentangling DOSY: Diffusion-ordered spectroscopy (DOSY) is an effective method for the analysis of intact mixtures, but the quality of results is critically limited by resolution in the NMR dimension. A new experiment integrating diffusion weighting into the PSYCHE method for pure shift NMR spectroscopy allows DOSY spectra to be measured with ultrahigh NMR resolution and improved sensitivity.

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Take the enantiopure and you will succeed: An octameric molecular capsule assembled through hydrogen bonds was synthesized by the strategy of chirality-assisted synthesis. Both ionic and neutral guests can be encapsulated within its 2300 ų cavity volume. The racemic starting material led to a mixture that also contained oligomeric and polymeric species.

[Communication]
Daniel Beaudoin, Frank Rominger, Michael Mastalerz
Angew. Chem. Int. Ed., November 10, 2016, DOI: 10.1002/anie.201609073. Read article

It's RNAs’ world: Geological strata show that Ca²⁺ does not take phosphate to form prebiotically unreactive apatite if borate, SO₄²⁻, and Mg²⁺ are present. Rather, phosphate is sequestered in the mineral lüneburgite. Upon evaporation, lüneburgite converts ribonucleosides regiospecifically to their phosphates. Thus, borate solves many problems in the synthesis of prebiotic RNA.

[Communication]
Hyo-Joong Kim, Yoshihiro Furukawa, Takeshi Kakegawa, Andrei Bita, Romulus Scorei, Steven A. Benner
Angew. Chem. Int. Ed., November 09, 2016, DOI: 10.1002/anie.201608001. Read article

One ring to rule them all … and in the darkness bind them: A photoresponsive tetracationic macrocycle features a facile three-step synthesis and makes possible the noncovalent binding of a set of guest molecules, including N-oxide and carboxylate derivatives. The guest molecules can be actively released by UV light irradiation in a remote fashion.

[Communication]
Seán T. J. Ryan, Jesús del Barrio, Reynier Suardíaz, Daniel F. Ryan, Edina Rosta, Oren A. Scherman
Angew. Chem. Int. Ed., October 28, 2016, DOI: 10.1002/anie.201607693. Read article

Nature Chemistry. doi:10.1038/nchem.2633

Authors: Hemakesh Mohapatra, Maya Kleiman & Aaron Palmer Esser-Kahn

Mechanochemically controlled polymerization is rare in polymer chemistry. Now, it has been shown that mechanical force can initiate and control the polymerization of an acrylate monomer. Piezochemical reduction of a copper(II) precursor using mechanical agitation of piezoelectric nanoparticles generates the polymerization activator required for controlled radical polymerization.