Biochemistry articles within Nature Communications

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  • Article
    | Open Access

    Advancements in plasma lipidomic profiling increase specificity of measurements but pose challenges in aligning datasets created at different times or platforms. Here the authors present a predictive framework for harmonising such datasets with different levels of granularity in their lipid measurements.

    • Aleksandar Dakic
    • , Jingqin Wu
    •  & Peter J. Meikle

  • Article
    | Open Access

    Gene variants can affect folding and stability of the encoded protein. Here, the authors apply deep mutational scanning to provide genotype-phenotype information for 99% of the possible PRKN variants and reveal mechanistic details on how some variants cause loss-of-function and Parkinsons disease.

    • Lene Clausen
    • , Vasileios Voutsinos
    •  & Rasmus Hartmann-Petersen

  • Article
    | Open Access

    Retinol, a form of vitamin A, plays an essential role in many biological processes throughout the human lifespan. Here the authors identify genetic variants that influence the level of circulating retinol and use this information to better understand how retinol impacts human health.

    • William R. Reay
    • , Dylan J. Kiltschewskij
    •  & Murray J. Cairns

  • Article
    | Open Access

    InsP3 3-kinase phosphorylates 1,4,5-trisphosphate (InsP3) specifically at its secondary 3-hydroxyl group to generate a tetrakisphosphate. Here, the authors used a combination of methods to survey InsP3 3-kinase ligand specificity and determined that IP3K specificity surpasses that of its natural substrate, allowing it to bind diverse ligands with a primary hydroxyl in the reactive position and based on a carbohydrate moiety.

    • María Ángeles Márquez-Moñino
    • , Raquel Ortega-García
    •  & Beatriz González

  • Article
    | Open Access

    CRISPR-Cas12a is a powerful RNA-guided genome-editing system. Saha et al. show that an alpha-helical lid plays the central role in guiding the target DNA toward the single RuvC nuclease domain, resulting in a double-stranded DNA break.

    • Aakash Saha
    • , Mohd Ahsan
    •  & Giulia Palermo

  • Article
    | Open Access

    The function of transcription factors is conveyed through intrinsically disordered regions (IDRs) containing activation or repression domains, but the lack of quantitative structural ensemble models prevents their mechanistic decoding. Here, the authors use several methods to demonstrate that DNA binding can lead to complex changes in the IDR ensemble and accessibility on the example of the C-terminal IDR of pioneer factor Sox2.

    • Sveinn Bjarnason
    • , Jordan A. P. McIvor
    •  & Pétur O. Heidarsson

  • Article
    | Open Access

    Mutations in rhodopsin can cause the receptor to aggregate, however, it is unclear whether this molecular defect underlies the retinal degeneration in autosomal dominant retinitis pigmentosa. Here, the authors show the potential for rhodopsin aggregates to play a role in retinal degeneration.

    • Sreelakshmi Vasudevan
    • , Subhadip Senapati
    •  & Paul S.–H. Park

  • Article
    | Open Access

    The importance of the SEL1L-HRD1 interaction in vivo was unclear. Here, authors reported that SEL1L-HRD1 interaction is required to form a functional HRD1 ERAD complex by recruiting the E2 enzyme UBE2J1 and DERLIN to HRD1.

    • Liangguang Leo Lin
    • , Huilun Helen Wang
    •  & Ling Qi

  • Article
    | Open Access

    The application of the LCC variant of polyethylene terephthalate (PET) hydrolase for industrial degradation of PET has been hindered by the 10% of nonbiodegradable PET. Here, the authors use a computational strategy to engineer TurboPETase which outperforms other PETase variants and achieves nearly complete depolymerization of the postconsumer PET bottles at a high, industrially relevant, level of solids loading.

    • Yinglu Cui
    • , Yanchun Chen
    •  & Bian Wu

  • Article
    | Open Access

    Paclitaxel is an important anticancer drug whose biosynthetic pathway reconstruction is hindered by the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, the authors tune the promoter strength for T5αH expression in Nicotiana plants to increase the levels of paclitaxel precursor taxadien-5α-ol by three-fold and reconstitute the six step early biosynthetic pathway of paclitaxel.

    • Jack Chun-Ting Liu
    • , Ricardo De La Peña
    •  & Elizabeth S. Sattely

  • Article
    | Open Access

    Here the authors discover a dedicated ribosome-associated chaperone, Chp1, that assists in the challenging biogenesis of eukaryotic translation elongation factor 1A (eEF1A) by cotranslationally stabilizing the growing GTPase domain of eEF1A.

    • Melania Minoia
    • , Jany Quintana-Cordero
    •  & Claes Andréasson

  • Article
    | Open Access

    Spontaneous activation of VEGFRs is a hallmark of diabetes and several cancers. Here, the authors show how in VEGFR1 a juxtamembrane segment connecting the catalytic and ligand-binding domains of the receptor can prevent its spontaneous activation.

    • Manas Pratim Chakraborty
    • , Diptatanu Das
    •  & Rahul Das

  • Article
    | Open Access

    Structural and functional studies highlight the molecular regulation of assembling the mitochondrial division machinery. The core unit is closed, and specific interactions open this unit to facilitate assembly at the right place and time in cells.

    • Kristy Rochon
    • , Brianna L. Bauer
    •  & Jason A. Mears

  • Article
    | Open Access

    Alzheimer’s plaques contain a high amount of Aβ fibrils and a high concentration of lipids. The authors determined structures of Aβ40 fibrils grown in the presence of lipids, revealing high-resolution details of potentially disease-relevant fibril-lipid interactions.

    • Benedikt Frieg
    • , Mookyoung Han
    •  & Gunnar F. Schröder

  • Article
    | Open Access

    The stoichiometry of Hrd1, an integral membrane E3 ubiquitin ligase is critical to maintaining proteostasis in the endoplasmic reticulum. Here, the authors establish a single-molecule counting approach coupled with a single-molecule in vitro ubiquitination system to determine the functional stoichiometry of Hrd1.

    • Basila Moochickal Assainar
    • , Kaushik Ragunathan
    •  & Ryan D. Baldridge

  • Article
    | Open Access

    The authors show G protein subtype selectivity at the β1-adrenergic receptor is driven by the binding kinetics of ternary complex formation. Bound to G protein, the receptor adopts conformations that differ from its agonist-bound solution states.

    • Andrew J. Y. Jones
    • , Thomas H. Harman
    •  & Daniel Nietlispach

  • Article
    | Open Access

    Poly-γ-glutamate tails are a distinctive feature of folate and F420 cofactors, but it was unclear how these tails elongate while maintaining substrate specificity. Here, the authors discover that folylpolyglutamate synthase and γ-glutamyl ligase enzymes add successive L-glutamates to the termini of the growing γ-glutamyl chain in a processive mechanism.

    • Ghader Bashiri
    • , Esther M. M. Bulloch
    •  & Christopher J. Squire

  • Article
    | Open Access

    Here the authors use NMR, SAXS and MD simulations to characterise the structure of proteusin peptides, which are atypically long RiPP substrates. They show a small, unstructured region in the proteusin leader is sufficient for its interaction with a halogenase that brominates the terminal tryptophan residue.

    • Nguyet A. Nguyen
    • , F. N. U. Vidya
    •  & Vinayak Agarwal

  • Article
    | Open Access

    Polyamides (PAs) or nylons are types of plastics with wide applications, but due to their accumulation in the environment, strategies for their deconstruction are of interest. Here, the authors screen 40 potential nylon-hydrolyzing enzymes (nylonases) using a mass spectrometry-based approach and identify a thermostabilized N-terminal nucleophile hydrolase as the most promising for further development, as well as crucial targets for progressing PA6 enzymatic depolymerization.

    • Elizabeth L. Bell
    • , Gloria Rosetto
    •  & Gregg T. Beckham

  • Article
    | Open Access

    Hemiacetal compounds are valuable building blocks in synthetic chemistry, but difficult to obtain by enzymatic synthesis. Here, the authors use reaction engineering of an immobilized unspecific peroxygenase from Agrocybe aegerita for selective C-H bond oxyfunctionalisation of environmentally significant cyclic ethers to chiral cyclic hemiacetals.

    • Xiaofeng Han
    • , Fuqiang Chen
    •  & Wuyuan Zhang

  • Article
    | Open Access

    Alzheimer’s Disease (AD) is commonly preceded by a prodromal period. Here, the authors report the presence of large plasma Aβ aggregates from patients with mild cognitive impairment, which associate with low level AD-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes.

    • Kristian Juul-Madsen
    • , Peter Parbo
    •  & Thomas Vorup-Jensen

  • Article
    | Open Access

    It is vital but challenging to develop coating technologies for addressing reliability and durability issues of electrochemical sensors when exposed to diverse and complex biological environments. Here, the authors report a micrometer-thick, porous and robust nanocomposite coating that enables highly sensitive and stable electrochemical sensors.

    • Jeong-Chan Lee
    • , Su Yeong Kim
    •  & Donald E. Ingber

  • Article
    | Open Access

    Do proteasomes catalyze peptide splicing? Here, the authors develop and apply a method to identify spliced peptides produced from entire proteins, confirm that proteasomes produce a sizeable variety of cis-spliced peptides with well-defined characteristics, and show that non-spliced and spliced peptides are concentrated in hotspots.

    • Wai Tuck Soh
    • , Hanna P. Roetschke
    •  & Michele Mishto

  • Article
    | Open Access

    GPR34 is a GPCR which has an immunomodulatory role and recognizes lysophosphatidylserine (LysoPS) as a putative endogenous ligand. Here, authors report two cryo-EM structures of human GPR34-Gi complex with one of two ligands bound: either the LysoPS analogue S3E-LysoPS, or its derivative M1.

    • Tamaki Izume
    • , Ryo Kawahara
    •  & Osamu Nureki

  • Article
    | Open Access

    NLRP3 is a critical intracellular inflammasome sensor and an important clinical target against inflammation-driven human diseases. Here, the authors determined Cryo-EM structures of human NLRP3 in its closed and open states, elucidating the mechanism of NLRP3 inflammasome activation.

    • Xiaodi Yu
    • , Rosalie E. Matico
    •  & Sujata Sharma

  • Article
    | Open Access

    Shigella enters human cells in a phagocytic vacuole and then escapes the vacuole to colonize the cytosol. Here, Chang and coworkers show that Shigella uses a bacterial effector to subvert host Rab proteins, microtubules and molecular motors to provide mechanical force to facilitate Shigella escape.

    • Yuen-Yan Chang
    • , Camila Valenzuela
    •  & John Rohde

  • Article
    | Open Access

    The ability to engineer novel protein structures has tremendous scientific and therapeutic impact. Here, authors develop a generative model acting upon an angular representation of protein structures to create high quality protein backbones.

    • Kevin E. Wu
    • , Kevin K. Yang
    •  & Ava P. Amini

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