Peptides articles within Nature Communications

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  • Article
    | Open Access

    Methods for peptide stapling, or covalently linking amino acid residues to create a non-linear structure, mostly rely on cysteine residues, which imposes a significant practical limitation. Here the authors disclose a method to chemoselectively macrocyclize two free-amine-containing residues in mild, peptide-relevant conditions, using a commercially available reagent.

    • Bo Li
    • , Lan Wang
    •  & Gong Chen

  • Article
    | Open Access

    Generic approach for rapid prototyping is essential for the progress of synthetic biology. Here the authors modify the cell-free translation system to control protein aggregation and folding and validate the approach by using single conditions for prototyping of various disulfide-constrained polypeptides.

    • Yue Wu
    • , Zhenling Cui
    •  & Sergey Mureev

  • Article
    | Open Access

    Chiral communication can propagate in secondary structures within the effective intermolecular force (IMF) range but it is not known whether long-range chiral communication exists between tertiary peptide structures. Here, the authors use single-molecule force spectroscopy to investigate chiral interaction between DNA duplexes/triplexes and peptide coiled-coils and demonstrate chiral communication beyond the IMF distance.

    • Shankar Pandey
    • , Shankar Mandal
    •  & Hanbin Mao

  • Article
    | Open Access

    AlphaFold2 has originally been developed to provide highly accurate predictions of protein monomer structures. Here, the authors present a simple adaptation of AlphaFold2 that enables structural modeling of peptide–protein complexes, and explore the underlying mechanisms and limitations of this approach.

    • Tomer Tsaban
    • , Julia K. Varga
    •  & Ora Schueler-Furman

  • Article
    | Open Access

    Here, we present TP-DB; a pattern-based search engine based on 1.67 million helices from the Protein Database (PDB). We demonstrate the utility of TP-DB in identifying microbe-specific antigens, as well as the design of antimicrobial peptides and Protein-protein interaction blockers.

    • Cheng-Yu Tsai
    • , Emmanuel Oluwatobi Salawu
    •  & Lee-Wei Yang

  • Article
    | Open Access

    Peptide bond formation is one of the key biochemical reactions needed for the formation of life, but is thermodynamically unfavoured in water. Here, the authors report on the possibility of complex oligomer formation in liquid sulphur dioxide which may have existed on early Earth at the emergence of life.

    • Fabian Sauer
    • , Maren Haas
    •  & Oliver Trapp

  • Article
    | Open Access

    Endogenous ACE2 is a receptor for SARS-CoV-2 and a recombinant soluble ACE2 protein can inhibit SARS-CoV-2 infection acting as a decoy. Here the authors show that B38-CAP, an ACE2-like enzyme but not a decoy for the virus, is protective against SARS-CoV-2-induced lung injury in animal models.

    • Tomokazu Yamaguchi
    • , Midori Hoshizaki
    •  & Keiji Kuba

  • Article
    | Open Access

    Antibiotic resistance in Staphylococcus aureus is associated with reduced neutrophil recruitment. Here, Payne et al. link formylated peptides, which act as chemoattractants for neutrophils, with the antibiotic vancomycin and show that these hybrid compounds improve clearance of S. aureus by neutrophils.

    • Jennifer A. E. Payne
    • , Julien Tailhades
    •  & Max J. Cryle

  • Article
    | Open Access

    Peptide mass fingerprinting is a traditional approach for protein identification by mass spectrometry. Here, the authors provide evidence that peptide mass fingerprinting is also feasible using FraC nanopores, demonstrating protein identification based on nanopore measurements of digested peptides.

    • Florian Leonardus Rudolfus Lucas
    • , Roderick Corstiaan Abraham Versloot
    •  & Giovanni Maglia

  • Article
    | Open Access

    Borosins are ribosomally encoded and posttranslationally modified peptide (RiPP) natural products featuring amide-backbone α-N-methylation. Here, the authors report the discovery and characterization of type IV borosin ‘split’ pathways encoding distinct, separate α-N-methyltransferases and precursor peptide substrates.

    • Fredarla S. Miller
    • , Kathryn K. Crone
    •  & Michael F. Freeman

  • Article
    | Open Access

    C-Glycosyl peptides/proteins are metabolically stable mimics of the native glycopeptides/proteins of great therapeutic potential, but their chemical synthesis is challenging. Here, the authors report a protocol for the synthesis of vinyl C-glycosyl amino acids and peptides, via a Ni-catalyzed reductive hydroglycosylation reaction of alkyne derivatives of amino acids and peptides with glycosyl bromides.

    • Yan-Hua Liu
    • , Yu-Nong Xia
    •  & Biao Yu

  • Article
    | Open Access

    Self-assembling peptides have a range of potential applications but developing self-assembling sequences can be challenging. Here, the authors report on a one-bead one-compound combinatorial library where fluorescence is used to detect the potential for self-assembly and identified candidates are evaluated.

    • Pei-Pei Yang
    • , Yi-Jing Li
    •  & Kit S. Lam

  • Article
    | Open Access

    α-Synuclein (αS) aggregation is a driver of several neurodegenerative disorders. Here, the authors identify a class of peptides that bind toxic αS oligomers and amyloid fibrils but not monomeric functional protein, and prevent further αS aggregation and associated cell damage.

    • Jaime Santos
    • , Pablo Gracia
    •  & Salvador Ventura

  • Article
    | Open Access

    Self-assembling peptides (SAPs) can be used to build biomaterials, but genetically encoded SAPs have rarely been used as building blocks in cells. Here, the authors design a SAP that can be genetically fused to target proteins to induce their intracellular clustering and modulate their signaling functions.

    • Takayuki Miki
    • , Taichi Nakai
    •  & Hisakazu Mihara

  • Article
    | Open Access

    Cyclic peptides are of particular interest due to their pharmacological properties, but their design for binding to a target protein is challenging. Here, the authors present a computational “anchor extension” methodology for de novo design of cyclic peptides that bind to the target protein with high affinity, and validate the approach by developing cyclic peptides that inhibit histone deacetylases 2 and 6.

    • Parisa Hosseinzadeh
    • , Paris R. Watson
    •  & David Baker

  • Article
    | Open Access

    MALDI-mass spectrometry imaging (MSI) can reveal the distribution of proteins in tissues but tools for protein identification and annotation are sparse. Here, the authors develop an open-source bioinformatic workflow for false discovery rate-controlled protein annotation and spatial mapping from MALDI-MSI data.

    • G. Guo
    • , M. Papanicolaou
    •  & A. C. Grey

  • Article
    | Open Access

    Developing molecules that emulate the properties of naturally occurring ice-binding proteins (IBPs) is a daunting challenge. Here, the authors demonstrate the use of phage display for the identification of short peptide mimics of IBPs, which resulted in the identification of a cyclic ice-binding peptide containing just 14 amino acids.

    • Corey A. Stevens
    • , Fabienne Bachtiger
    •  & Harm-Anton Klok

  • Article
    | Open Access

    Methods for selective modification of the N-terminus of proteins are of high interest, but mostly require specific amino acid residues. Here, the authors report a selective and fast method for N-terminal modification of proteins based on quinone-mediated oxidation of the alpha-amine to aldehyde or ketone, and apply it to diverse proteins.

    • Siyao Wang
    • , Qingqing Zhou
    •  & Ping Wang

  • Article
    | Open Access

    14-3-3 proteins recognize phosphorylated motifs within numerous protein partners. Here, the authors characterize the binding of all human 14-3-3 isoforms to four E6 oncoproteins, and identify a fixed order of 14-3-3 binding affinities that is conserved in 14-3-3:phosphoprotein interactions across the proteome.

    • Gergo Gogl
    • , Kristina V. Tugaeva
    •  & Nikolai N. Sluchanko

  • Article
    | Open Access

    RaPID (Random non-standard Peptides Integrated Discovery) enables discovery of small macrocyclic peptides binding desired targets. Here, the authors propose lasso-grafting: the RaPID-derived peptides are implanted onto diverse proteins and maintain both the binding properties of the cyclic peptide and the host protein function.

    • Emiko Mihara
    • , Satoshi Watanabe
    •  & Junichi Takagi

  • Article
    | Open Access

    Many alternative ORFs are co-encoded with characterized proteins, but their function is often not understood. Here, the authors discover that ribosomal protein L36 is co-encoded with alternative protein, which they identify as an upstream regulator of PI3K-AKT-mTOR signaling.

    • Xiongwen Cao
    • , Alexandra Khitun
    •  & Sarah A. Slavoff

  • Article
    | Open Access

    Apelin and AVP have opposing effects water balance in humans and rodents. Here, the authors report that a metabolically stable apelin-17 analog, by acting at the kidney level, reduces AVP-induced antidiuresis and improves hyponatremia in rodents, demonstrating a potential approach for treating water metabolism disorders.

    • Adrien Flahault
    • , Pierre-Emmanuel Girault-Sotias
    •  & Catherine Llorens-Cortes

  • Article
    | Open Access

    FR900359 (FR) is a Gq protein inhibitor depsipeptide isolated from an uncultivable plant endosymbiont and synthesized by non-ribosomal peptide synthetases. Here, the authors discover a cultivable bacterial FR producer and show that FrsA thioesterase domain catalyses intermolecular transesterification of the FR side chain to the depsipeptide core during biosynthesis, improving Gq inhibition properties.

    • Cornelia Hermes
    • , René Richarz
    •  & Max Crüsemann

  • Article
    | Open Access

    Current histone microarrays cannot be used to directly study the transient interactions of histone deacetylases (HDACs). Here, the authors show that hydroxamic acid-modified microarrays can capture HDACs, provide insights into their substrate specificity, and serve to develop peptide inhibitors.

    • Carlos Moreno-Yruela
    • , Michael Bæk
    •  & Christian A. Olsen

  • Article
    | Open Access

    The development of specific anti-cytokine/chemokine therapeutic strategies for atherosclerotic disease is challenging. Here, the authors have designed a peptide-based ectodomain mimic of the chemokine receptor CXCR4 that selectively targets MIF but not CXCL12 and blocks experimental atherosclerosis in vivo.

    • Christos Kontos
    • , Omar El Bounkari
    •  & Jürgen Bernhagen

  • Article
    | Open Access

    ADP-ribosylated peptides are important molecular tools, however, the lack of effective synthetic methods hinders the access to their complex structures. Here, the authors present a biomimetic α-selective ribosylation reaction coupled with click chemistry ultimately providing a two-step modular synthesis of α-ADP-ribosylated peptides.

    • Anlian Zhu
    • , Xin Li
    •  & Lingjun Li

  • Article
    | Open Access

    Targeting the interaction between transcription factor TEAD and its co-repressor VGL4 is an attractive strategy to chemically modulate Hippo signaling. Here, the authors develop a proteomimetic with stabilized tertiary structure that inhibits the TEAD:VGL4 interaction in vitro and in cells.

    • Hélène Adihou
    • , Ranganath Gopalakrishnan
    •  & Herbert Waldmann

  • Article
    | Open Access

    Oxepinamides are a class of fungal oxepins with biological activities. Here, the authors elucidate the biosynthetic pathway of oxepinamide F from Aspergillus ustus and show that it involves enyme-catalysed oxepin ring formation, hydroxylation-induced double bond migration, epimerization and methylation.

    • Liujuan Zheng
    • , Haowen Wang
    •  & Shu-Ming Li

  • Article
    | Open Access

    Backbone extended monomers are poorly compatible with the natural ribosomes, impeding their polymerization into polypeptides. Here the authors design non-canonical amino acid analogs with cyclic structures or extended carbon chains and used an engineered ribosome to improve tRNA-charging and incorporation into peptides.

    • Joongoo Lee
    • , Kevin J. Schwarz
    •  & Michael C. Jewett

  • Article
    | Open Access

    Mass spectrometry-based proteomics is the method of choice for the global mapping of post-translational modifications, but matching and scoring peaks with unknown masses remains challenging. Here, the authors present a refined open search strategy to score all peaks with higher sensitivity and accuracy.

    • Fengchao Yu
    • , Guo Ci Teo
    •  & Alexey I. Nesvizhskii

  • Article
    | Open Access

    Mitochondrial apoptosis is controlled by BCL2 family proteins, and the BH3-only proteins often act as sensors that transmit apoptotic signals. Here the authors show how the BH3-only proteins BMF and HRK can directly activate the BCL2 protein BAK and interact with BAK through an alternative binding groove.

    • Kaiqin Ye
    • , Wei X. Meng
    •  & Haiming Dai

  • Article
    | Open Access

    Synthetic peptide libraries can access broad chemical space, but generally examine only ~ 106 compounds. Here, the authors show that in-solution affinity selection, interfaced with nLC-MS/MS sequencing, can identify binders from fully randomized synthetic libraries of 108 members.

    • Anthony J. Quartararo
    • , Zachary P. Gates
    •  & Bradley L. Pentelute

  • Article
    | Open Access

    Sequestration of reactants in lipid vesicles is a strategy prevalent in biological systems to raise the rate and specificity of chemical reactions. Here, the authors show that micelle-assisted reactions facilitate native chemical ligation between a peptide-thioester and a Cys-peptide modified by a lipid-like moiety.

    • Shuaijiang Jin
    • , Roberto J. Brea
    •  & Neal K. Devaraj

  • Article
    | Open Access

    Immunopeptidomics allows identifying the cellular repertoire of MHC-bound peptides, but quantifying them remains challenging. Here, the authors present a method to efficiently generate internal peptide MHC standards and calibration curves, facilitating relative and absolute quantitative immunopeptidomics.

    • Lauren E. Stopfer
    • , Joshua M. Mesfin
    •  & Forest M. White

  • Article
    | Open Access

    Trefoil factors (TFFs) protect the mucosa and have various reported binding activities, but whether they share a common interaction mechanism has remained unclear. Here, the authors provide structural and biochemical evidence that all three human TFFs are divalent lectins that recognise the same disaccharide.

    • Michael A. Järvå
    • , James P. Lingford
    •  & Ethan D. Goddard-Borger

  • Article
    | Open Access

    Antibodies conjugated to bioactive compounds can allow targeted delivery of therapeutics. Here the authors present a strategy for fusing nanobodies to suboptimal GPCR peptide ligands to potently and selectively activate receptors.

    • Ross W. Cheloha
    • , Fabian A. Fischer
    •  & Hidde L. Ploegh

  • Article
    | Open Access

    NF-κB signalling involves the scaffold protein NEMO, which can be bound by the oncoprotein vFLIP to promote cell survival and oncogenic transformation. Here the authors rationally engineer a tertiary protein mimic of NEMO to disrupt the vFLIP-NEMO interaction to induce cell death.

    • Jouliana Sadek
    • , Michael G. Wuo
    •  & Paramjit S. Arora

  • Article
    | Open Access

    Asparaginyl endopeptidases (AEPs) catalyze the cyclization step during the biosynthesis of cyclic peptides in plants. Here, the authors report a recombinantly produced AEP that catalyzes the backbone cyclization of a linear cyclotide precursor and an engineered analog with high efficiency and in a pH-dependent manner.

    • Junqiao Du
    • , Kuok Yap
    •  & David J. Craik

  • Article
    | Open Access

    Most epigenetic regulator inhibitors target tunnels of active sites, rather than the peptide binding groove, leading to concerns with low selectivity. Here the authors use an amber obligate phage library to rapidly identify isoform-selective inhibitors of SIRT2.

    • Jeffery M. Tharp
    • , J. Trae Hampton
    •  & Wenshe Ray Liu

  • Article
    | Open Access

    Non-canonical HLA-bound peptides from presumed non-coding regions are potential targets for cancer immunotherapy, but their discovery remains challenging. Here, the authors integrate exome sequencing, transcriptomics, ribosome profiling, and immunopeptidomics to identify tumor-specific non-canonical HLA-bound peptides.

    • Chloe Chong
    • , Markus Müller
    •  & Michal Bassani-Sternberg

  • Article
    | Open Access

    Cystine-knot miniprotein are small, highly stable, disulfide-rich peptides with increasing potential as drugs and tumor imaging agents. Here the authors develop cystine-knot miniproteins targeting the vascular tumor marker EDB, and use them as probes for in vivo tumor vasculature imaging.

    • Bonny Gaby Lui
    • , Nadja Salomon
    •  & Ugur Sahin

  • Article
    | Open Access

    Acetylation of p53 is critical for its transcriptional activity and its tumour suppressive function. Here, the authors show that PBRM1 is a reader protein for p53′s C-terminal domain acetylation on lysine 382 through its bromodomain 4 and that mutations in this domain leads to compromised tumour suppressive function and renal tumour growth.

    • Weijia Cai
    • , Liya Su
    •  & Haifeng Yang

  • Article
    | Open Access

    Chiral inversion of amino acids is thought to modulate the structure and function of amyloid beta (Aβ) but these processes are poorly understood. Here, the authors develop an ion mobility-mass spectrometry based approach to study chirality-regulated structural features of Aβ fragments and their influence on receptor recognition.

    • Gongyu Li
    • , Kellen DeLaney
    •  & Lingjun Li

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