Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    The pathogenic oomycete Saprolegnia parasitica secretes effector proteins that translocate into host cells through unclear mechanisms. Here, Trusch et al. show that the uptake of effector protein SpHtp3, resulting in RNA degradation, depends on a gp96-like host receptor and a second effector protein.

    • Franziska Trusch
    • , Lars Loebach
    •  & Pieter van West
  • Article
    | Open Access

    The export of mRNA to the cytosol depends on the nuclear pore complex (NPC) and the activation of the helicase DDX19, but their interplay in humans remains poorly understood. Here, the authors present a structural and functional analysis of DDX19 activation, revealing how the human NPC regulates mRNA export.

    • Daniel H. Lin
    • , Ana R. Correia
    •  & André Hoelz
  • Article
    | Open Access

    Mutations in the cation channel PKD2 cause human autosomal dominant polycystic kidney disease but its channel function and gating mechanism are poorly understood. Here authors study PKD2 using electrophysiology and cryo-EM, which identifies hydrophobic gates and proposes a gating mechanism for PKD2.

    • Wang Zheng
    • , Xiaoyong Yang
    •  & Xing-Zhen Chen
  • Article
    | Open Access

    So far little is known about how encapsulation affects the activity and folding of RNA, which is of interest for understanding the origin of cellular life. Here the authors show that encapsulation of functional RNA in vesicles increases RNA activity and improves RNA folding through a biophysical confinement effect.

    • Ranajay Saha
    • , Samuel Verbanic
    •  & Irene A. Chen
  • Article
    | Open Access

    Development of biocatalysts that mimic compartmentalized reactions in cells has been cumbersome due to the lack of low-cost materials and associated technologies. Here the authors show that cationic lignin nanospheres function as activating anchors for hydrolases, and enable aqueous ester synthesis by forming spatially confined biocatalysts.

    • Mika Henrikki Sipponen
    • , Muhammad Farooq
    •  & Monika Österberg
  • Article
    | Open Access

    During atherosclerosis, endothelial cells release purines in response to oxidized phospholipids. Here, Hitzel et al. show that oxidized phospholipids activate an MTHFD2-regulated gene network in endothelial cells which reprograms amino acid metabolism towards production of purines and thus compensates for their loss.

    • Juliane Hitzel
    • , Eunjee Lee
    •  & Ralf P. Brandes
  • Article
    | Open Access

    The human enzyme MTHFR links the folate and methionine cycles, which are essential for the biosynthesis of nucleotides and proteins. Here, the authors present the crystal structure and biochemical analysis of human MTHFR, providing molecular insights into its function and regulation in higher eukaryotes.

    • D. Sean Froese
    • , Jolanta Kopec
    •  & Wyatt W. Yue
  • Article
    | Open Access

    It remains poorly understood how a single RNA-binding protein recognizes diverse RNA targets. Here the authors use an integrative approach to study the binding of spliceosomal SNF protein to U1 and U2 small nuclear RNAs in the presence or absence of auxiliary protein U2A’ and show how SNF’s conformational dynamics are tuned to recognize different stem-loop structures.

    • Gert Weber
    • , Gregory T. DeKoster
    •  & Markus C. Wahl
  • Article
    | Open Access

    Pentatricopeptide repeat proteins bind single-stranded RNA and have been used to study ssRNA biology. Here the authors co-opt these proteins to target ssDNA and demonstrate specific binding of telomere sequences, the structural basis for ssDNA wrapping, and use them as potent telomerase inhibitors.

    • Henrik Spåhr
    • , Tiongsun Chia
    •  & Oliver Rackham
  • Article
    | Open Access

    Mutations in the RNA component TERC can cause telomerase dysfunction but the underlying mechanisms are largely unknown. Here, the authors show that RNA-binding protein HuR regulates telomerase function by enhancing the methylation of TERC, which is impaired by several disease-relevant TERC mutations.

    • Hao Tang
    • , Hu Wang
    •  & Wengong Wang
  • Article
    | Open Access

    The ribosome-associated quality control complex (RQC) functions to disassemble stalled ribosomes. Here the authors find that the tRNA hydrolase Vms1 is involved in the release of nascent peptide from stalled ribosomes.

    • Olga Zurita Rendón
    • , Eric K. Fredrickson
    •  & Jared Rutter
  • Article
    | Open Access

    Synthetic prions have previously been generated from recombinant rodent PrP. Here the authors generate synthetic human prions, by seeding human PrP with CJD prions, and characterize its infectivity in mice.

    • Chae Kim
    • , Xiangzhu Xiao
    •  & Jiri G. Safar
  • Article
    | Open Access

    The bacterial protein disaggregation machine ClpB uses ATP to generate mechanical force to unfold and thread its protein substrates. Here authors visualize the ClpB ring using high-speed atomic force microscopy and capture conformational changes of the hexameric ring during the ATPase reaction.

    • Takayuki Uchihashi
    • , Yo-hei Watanabe
    •  & Toshio Ando
  • Article
    | Open Access

    The concentration of divalent cations is well-known to influence molecular processes such as enzymatic activity and RNA folding. Here the authors attempt to reproduce physiological conditions for RNA folding in vitro and establish an important contribution of chelated magnesium ions in enhancing RNA function.

    • Ryota Yamagami
    • , Jamie L. Bingaman
    •  & Philip C. Bevilacqua
  • Review Article
    | Open Access

    Temporary association of metabolic enzymes is generally assumed to facilitate substrate channelling within the complex. In this review, Lee Sweetlove and Alisdair Fernie outline the nature and functional consequence of organising enzymes into assemblies, and discuss applications within the natural world and synthetic biology.

    • Lee J. Sweetlove
    •  & Alisdair R. Fernie
  • Article
    | Open Access

    R2TP is an HSP90 co-chaperone composed of an RPAP3-PIH1D1 heterodimer, which binds two essential AAA+ ATPases RUVBL1/RUVBL2. Here authors use a structural approach to study RPAP3 and find an RPAP3-like protein (SPAG1) which also forms a co-chaperone complex with PIH1D2 and RUVBL1/2 enriched in testis.

    • Chloé Maurizy
    • , Marc Quinternet
    •  & Edouard Bertrand
  • Article
    | Open Access

    The p53-binding protein 1 (53BP1) regulates the choice of the DNA double-strand break repair pathway. Here the authors present the crystal structure of Tudor-interacting repair regulator (TIRR) bound to the 53BP1 tandem Tudor domain, which reveals how TIRR blocks H4K20me2 binding to 53BP1 Tudor and functionally differs from its paralog Nudt16.

    • Yaxin Dai
    • , Aili Zhang
    •  & Zheng Zhou
  • Article
    | Open Access

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder with no present cure. Here the authors perform an in vitro screening leading to the identification of a small molecule that alters the conformational dynamics of the TSL2 RNA structure and acts as a modulator of SMN exon 7 splicing.

    • Amparo Garcia-Lopez
    • , Francesca Tessaro
    •  & Leonardo Scapozza
  • Article
    | Open Access

    Many bacterial proteins exhibit spatially defined localization important for function. Here the authors show that the polar localization of Shigella IpaC type III secretion substrate is mediated by its interaction with the DnaK chaperone and occlusion by the bacterial nucleoid.

    • Clémence Collet
    • , Jenny-Lee Thomassin
    •  & Guy Tran Van Nhieu
  • Article
    | Open Access

    Artificial compartments have been expressed in prokaryotes and yeast, but similar capabilities have been missing for mammalian cell engineering. Here the authors use bacterial encapsulins to engineer genetically controlled multifunctional orthogonal compartments in mammalian cells.

    • Felix Sigmund
    • , Christoph Massner
    •  & Gil G. Westmeyer
  • Article
    | Open Access

    Photobiodevices use photosynthetic proteins such as those of the photosystem 1 (PS1) to enable light-induced charge separation, but they suffer from limited long-term stability. Here authors employ scanning photoelectrochemical microscopy on a PS1 biocathode and find that several pathways generate oxygen radicals.

    • Fangyuan Zhao
    • , Steffen Hardt
    •  & Felipe Conzuelo
  • Article
    | Open Access

    Kynurenine is an immunomodulatory aryl hydrocarbon receptor (AHR) ligand. Here the authors show, using a new flow cytometry based method, that kynurenine needs to be transported across the plasma membrane of activated T cells by the transporter protein SLC7A5 to activate the AHR.

    • Linda V. Sinclair
    • , Damien Neyens
    •  & Doreen A. Cantrell
  • Article
    | Open Access

    The 3-thiazolidine ring, a pharmaceutically interesting cyclic structural element found e.g. in some antibiotics, is hard to obtain via currently used approaches. Here, the authors developed a straightforward method to efficiently synthesize a variety of defined, pure 3-thiazolidines.

    • Nadine Zumbrägel
    • , Christian Merten
    •  & Harald Gröger
  • Article
    | Open Access

    Endoglycosidase S only recognizes one particular type of glycan within IgG antibodies but the molecular basis for this high specificity is not fully understood. Here, the authors present the crystal structure of product-bound Endoglycosidase S, revealing the determinants for its glycan specificity.

    • Beatriz Trastoy
    • , Erik Klontz
    •  & Marcelo E. Guerin
  • Article
    | Open Access

    Transfer RNA modifications play critical roles in protein synthesis. Here the authors reveal the t6A37 tRNA modification is dynamically regulated by sensing intracellular CO2 concentration in mitochondria, implying metabolic regulation of protein synthesis.

    • Huan Lin
    • , Kenjyo Miyauchi
    •  & Tsutomu Suzuki
  • Article
    | Open Access

    Cofilin is a small actin-binding protein that accelerates actin turnover by disassembling actin filaments. Here the authors present the 3.8 Å cryo-EM structure of a cofilin-decorated actin filament and discuss mechanistic implications.

    • Kotaro Tanaka
    • , Shuichi Takeda
    •  & Akihiro Narita
  • Article
    | Open Access

    The structures of amyloid fibres are currently primarily studied through solid state NMR and cryo-EM. Here the authors present a free-standing graphene support device that allows diffraction imaging of non-crystalline amyloid fibrils with single X-ray pulses from an X-ray free-electron laser.

    • Carolin Seuring
    • , Kartik Ayyer
    •  & Henry N. Chapman
  • Article
    | Open Access

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor. Here the authors provide insights into PPARγ activation by combining fluorine (19F) NMR and molecular dynamics simulations to characterize the nuclear receptor conformational ensemble in solution and the response of this ensemble to ligand and coregulatory peptide binding.

    • Ian M. Chrisman
    • , Michelle D. Nemetchek
    •  & Travis S. Hughes
  • Article
    | Open Access

    Small nucleolar ribonucleoprotein complexes (snoRNP) are fundamental for ribosome biogenesis. Here the authors provide insight into the 5ʹend processing of S. cerevisiae snoRNA and its important role in downstream nuclear events.

    • Pawel Grzechnik
    • , Sylwia A. Szczepaniak
    •  & Nicholas J. Proudfoot
  • Article
    | Open Access

    It remains poorly understood whether and how chaperones control protein evolution. Here the authors show how the chaperone Hsp90 shapes the sequence space of its client, poliovirus protein P1, at the polypeptide and RNA level to balance the evolutionary trade-offs between protein stability, aggregation and translation rate.

    • Ron Geller
    • , Sebastian Pechmann
    •  & Judith Frydman
  • Article
    | Open Access

    Sialic acid transporters (SiaT) are required for sialic acid uptake in a number of human pathogens and are of interest as targets for antimicrobial drug development. Here the authors present the substrate bound SiaT structure from the uropathogen Proteus mirabilis and provide insights into the mechanism of sialic acid transport.

    • Weixiao Y. Wahlgren
    • , Elin Dunevall
    •  & Rosmarie Friemann
  • Article
    | Open Access

    The spliceosome removes introns from precursor messenger RNAs to produce mature mRNAs. Here the authors report a U6 snRNP crystal structure that provides insight on how the 3′ phosphate of U6 snRNA is recognized by the Lsm2–8 complex and how the U6 snRNP proteins sequester and protect the active site RNA until it is assembled into the spliceosome.

    • Eric J. Montemayor
    • , Allison L. Didychuk
    •  & Samuel E. Butcher