Papain-like cysteine proteases prepare plant cyclic peptide precursors for cyclization.

Abstract:

:Cyclotides are plant defense peptides that have been extensively investigated for pharmaceutical and agricultural applications, but key details of their posttranslational biosynthesis have remained elusive. Asparaginyl endopeptidases are crucial in the final stage of the head-to-tail cyclization reaction, but the enzyme(s) involved in the prerequisite steps of N-terminal proteolytic release were unknown until now. Here we use activity-guided fractionation to identify specific members of papain-like cysteine proteases involved in the N-terminal cleavage of cyclotide precursors. Through both characterization of recombinantly produced enzymes and in planta peptide cyclization assays, we define the molecular basis of the substrate requirements of these enzymes, including the prototypic member, here termed kalatase A. The findings reported here will pave the way for improving the efficiency of plant biofactory approaches for heterologous production of cyclotide analogs of therapeutic or agricultural value.

authors

Rehm FBH,Jackson MA,De Geyter E,Yap K,Gilding EK,Durek T,Craik DJ

doi

10.1073/pnas.1901807116

subject

Has Abstract

pub_date

2019-04-16 00:00:00

pages

7831-7836

issue

16

eissn

0027-8424

issn

1091-6490

pii

1901807116

journal_volume

116

pub_type

杂志文章
  • Direct demonstration of the isomerization component of the monoterpene cyclase reaction using a cyclopropylcarbinyl pyrophosphate substrate analog.

    abstract::The tightly coupled nature of the reaction sequence catalyzed by monoterpene cyclases has precluded direct observation of the topologically required isomerization step leading from geranyl pyrophosphate to the presumptive, enzyme-bound, tertiary allylic intermediate linalyl pyrophosphate, which ultimately cyclizes to ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.14.4856

    authors: Wheeler CJ,Croteau RB

    更新日期:1987-07-01 00:00:00

  • Disease-associated mutant alpha-actinin-4 reveals a mechanism for regulating its F-actin-binding affinity.

    abstract::Alpha-actinin-4 is a widely expressed protein that employs an actin-binding site with two calponin homology domains to crosslink actin filaments (F-actin) in a Ca(2+)-sensitive manner in vitro. An inherited, late-onset form of kidney failure is caused by point mutations in the alpha-actinin-4 actin-binding domain. Her...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0702451104

    authors: Weins A,Schlondorff JS,Nakamura F,Denker BM,Hartwig JH,Stossel TP,Pollak MR

    更新日期:2007-10-09 00:00:00

  • Nonexponential kinetics of a single tRNAPhe molecule under physiological conditions.

    abstract::The fluorescence decay functions of individual, specifically labeled tRNAPhe molecules exhibit nonexponential character as a result of conformational dynamics occurring during the measurement on a single molecule. tRNAPhe conformational states that interchange much more slowly are evidenced by the distribution of life...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.15.7932

    authors: Jia Y,Sytnik A,Li L,Vladimirov S,Cooperman BS,Hochstrasser RM

    更新日期:1997-07-22 00:00:00

  • Phenotypic conversion of drug-resistant bacteria to drug sensitivity.

    abstract::Plasmids that contain synthetic genes coding for small oligoribonucleotides called external guide sequences (EGSs) have been introduced into strains of Escherichia coli harboring antibiotic resistance genes. The EGSs direct RNase P to cleave the mRNAs transcribed from these genes thereby converting the phenotype of dr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.16.8468

    authors: Guerrier-Takada C,Salavati R,Altman S

    更新日期:1997-08-05 00:00:00

  • GABAB receptor deficiency causes failure of neuronal homeostasis in hippocampal networks.

    abstract::Stabilization of neuronal activity by homeostatic control systems is fundamental for proper functioning of neural circuits. Failure in neuronal homeostasis has been hypothesized to underlie common pathophysiological mechanisms in a variety of brain disorders. However, the key molecules regulating homeostasis in centra...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1424810112

    authors: Vertkin I,Styr B,Slomowitz E,Ofir N,Shapira I,Berner D,Fedorova T,Laviv T,Barak-Broner N,Greitzer-Antes D,Gassmann M,Bettler B,Lotan I,Slutsky I

    更新日期:2015-06-23 00:00:00

  • DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes.

    abstract::Recent findings intriguingly place DNA double-strand break repair proteins at chromosome ends in yeast, where they help maintain normal telomere length and structure. In the present study, an essential telomere function, the ability to cap and thereby protect chromosomes from end-to-end fusions, was assessed in repair...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.26.14899

    authors: Bailey SM,Meyne J,Chen DJ,Kurimasa A,Li GC,Lehnert BE,Goodwin EH

    更新日期:1999-12-21 00:00:00

  • Inactivation of ethanol-inducible cytochrome P450 and other microsomal P450 isozymes by trans-4-hydroxy-2-nonenal, a major product of membrane lipid peroxidation.

    abstract::Of the microsomal P450 cytochromes, the ethanol-inducible isoform, P450 2E1, is believed to be predominant in leading to oxidative damage, including the generation of radical species that contribute to lipid peroxidation, and in the reductive beta-scission of lipid hydroperoxides to give hydrocarbons and aldehydes. In...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.9.3764

    authors: Bestervelt LL,Vaz AD,Coon MJ

    更新日期:1995-04-25 00:00:00

  • phiX174 DNA-dependent DNA synthesis in vitro: requirement for P1 ban protein in dnaB mutant extracts of Escherichia coli.

    abstract::Ammonium sulfate fractionation of crude extracts of E. coli yields a soluble enzyme fraction (about 25-fold purification) that catalyzes the conversion of phiX174 single-stranded DNA to duplex DNA. The reaction is rifampicin-resistant, requires single-stranded DNA, Mg++, deoxynucleoside triphosphates, and ATP, and is ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.10.3907

    authors: Schuster H,Mikolajczyk M,Rohrschneider J,Geschke B

    更新日期:1975-10-01 00:00:00

  • Internal homologies in the two aspartokinase-homoserine dehydrogenases of Escherichia coli K-12.

    abstract::In Escherichia coli, AK I- HDH I and AK II- HDH II are two bifunctional proteins, derived from a common ancestor, that catalyze the first and third reactions of the common pathway leading to threonine and methionine. An extensive amino acid sequence comparison of both molecules reveals two main features on each of the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.10.3019

    authors: Ferrara P,Duchange N,Zakin MM,Cohen GN

    更新日期:1984-05-01 00:00:00

  • Analysis of viral DNA sequences in hamster cells transformed by herpes simplex virus type 2.

    abstract::Herpes simplex virus type 2 (HSV-2) DNA was treated with four restriction endonucleases (EcoRI, HincIII, Bgl II, and Xba I) and eight fragments were purified and labeled with 32P in vitro. The kinetics of renaturation of each of the fragments was measured in the presence of DNA extracted from 333-8-9, a hamster cell l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.2.880

    authors: Galloway DA,Copple CD,McDougall JK

    更新日期:1980-02-01 00:00:00

  • Does vegetation prevent wave erosion of salt marsh edges?

    abstract::This study challenges the paradigm that salt marsh plants prevent lateral wave-induced erosion along wetland edges by binding soil with live roots and clarifies the role of vegetation in protecting the coast. In both laboratory flume studies and controlled field experiments, we show that common salt marsh plants do no...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0901297106

    authors: Feagin RA,Lozada-Bernard SM,Ravens TM,Möller I,Yeager KM,Baird AH

    更新日期:2009-06-23 00:00:00

  • Identification of a gene for the alpha-subunit of RNA polymerase at the str-spc region of the Escherichia coli chromosome.

    abstract::A structural gene for the alpha-subunit of RNA polymerase (nucleosidetriphosphate:RNA nucleotidyltransferase; EC 2.7.7.6) has been identified and mapped between spcA and trkA, near 64 min on the E. coli chromosome. It appears to be coordinately expressed and possibly cotranscribed with the genes for ribosomal proteins...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.12.5036

    authors: Jaskunas SR,Burgess RR,Nomura M

    更新日期:1975-12-01 00:00:00

  • From the Cover: Antarctic climate signature in the Greenland ice core record.

    abstract::A numerical algorithm is applied to the Greenland Ice Sheet Project 2 (GISP2) dust record from Greenland to remove the abrupt changes in dust flux associated with the Dansgaard-Oeschger (D-O) oscillations of the last glacial period. The procedure is based on the assumption that the rapid changes in dust are associated...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0708494104

    authors: Barker S,Knorr G

    更新日期:2007-10-30 00:00:00

  • Substrate free radicals are intermediates in ligninase catalysis.

    abstract::The H2O2-requiring ligninase of the basidiomycete Phanerochaete chrysosporium oxidatively cleaves both lignin and lignin model compounds between C alpha and C beta (C-1 and C-2) of their aliphatic side chains. Previous work has demonstrated a reaction mechanism by which ligninase oxidizes aromatic substrates to their ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.11.3708

    authors: Hammel KE,Kalyanaraman B,Kirk TK

    更新日期:1986-06-01 00:00:00

  • Multiscale natural moves refine macromolecules using single-particle electron microscopy projection images.

    abstract::The method presented here refines molecular conformations directly against projections of single particles measured by electron microscopy. By optimizing the orientation of the projection at the same time as the conformation, the method is well-suited to two-dimensional class averages from cryoelectron microscopy. Suc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1205945109

    authors: Zhang J,Minary P,Levitt M

    更新日期:2012-06-19 00:00:00

  • Monoclonal antibodies against trophectoderm-specific markers during mouse blastocyst formation.

    abstract::Two-dimensional gel electrophoresis has allowed the detection of proteins characteristic of inner cell mass and trophectoderm in mouse blastocyst. Certain of the proteins characterizing trophectoderm copurify with intermediate filaments from trophectoderm and a trophoblastoma cell line. A monoclonal antibody prepared ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.7.4113

    authors: Brûlet P,Babinet C,Kemler R,Jacob F

    更新日期:1980-07-01 00:00:00

  • Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation.

    abstract::Delayed implantation (embryonic diapause) occurs when the embryo at the blastocyst stage achieves a state of suspended animation. During this period, blastocyst growth is very slow, with minimal or no cell division. Nearly 100 mammals in seven different orders undergo delayed implantation, but the underlying molecular...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0402597101

    authors: Hamatani T,Daikoku T,Wang H,Matsumoto H,Carter MG,Ko MS,Dey SK

    更新日期:2004-07-13 00:00:00

  • Nondiffusive mechanisms enhance protein uptake rates in ion exchange particles.

    abstract::Scanning confocal fluorescence microscopy and multiphoton fluorescence microscopy were used to image the uptake of the protein lysozyme into individual ion exchange chromatography particles in a packed bed in real time. Self-sharpening concentration fronts penetrating into the particles were observed at low salt conce...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0237084100

    authors: Dziennik SR,Belcher EB,Barker GA,DeBergalis MJ,Fernandez SE,Lenhoff AM

    更新日期:2003-01-21 00:00:00

  • Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby.

    abstract::DNA mismatch repair (MMR), the guardian of the genome, commences when MutS identifies a mismatch and recruits MutL to nick the error-containing strand, allowing excision and DNA resynthesis. Dominant MMR models posit that after mismatch recognition, ATP converts MutS to a hydrolysis-independent, diffusive mobile clamp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1918517117

    authors: Hao P,LeBlanc SJ,Case BC,Elston TC,Hingorani MM,Erie DA,Weninger KR

    更新日期:2020-07-28 00:00:00

  • Hybrid H-2 histocompatibility gene products assign domains recognized by alloreactive T cells.

    abstract::In vitro recombination of cloned H-2 genes resulted in two allogeneically novel mouse transplantation antigens in which the C2 domains of H-2Ld and H-2Dd were exchanged. These genes were introduced into mouse L cells by DNA-mediated gene transfer. We have used these transformed fibroblast lines, expressing recombinant...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.7.2040

    authors: Ozato K,Evans GA,Shykind B,Margulies DH,Seidman JG

    更新日期:1983-04-01 00:00:00

  • DNA supercoiling affects in vitro transcription of two maize chloroplast genes differently.

    abstract::Two adjacent, divergently transcribed, developmentally regulated genes of the maize chloroplast chromosome have different superhelical density/transcriptional activation profiles when transcribed in vitro by the homologous DNA-dependent RNA polymerase. Promoter-specific transcription of the gene for the beta and epsil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.15.4886

    authors: Stirdivant SM,Crossland LD,Bogorad L

    更新日期:1985-08-01 00:00:00

  • Temperature and manganese as determining factors in the presence of diatom or blue-green algal floras in streams.

    abstract::Diatoms are usually the major component of the algal flora in many streams, although green and blue-green algae may be present. These experiments were designed to determine if high temperature or a shift in the chemical composition of the water might bring about a dominance of blue-green algae and/or green algae rathe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.64.2.472

    authors: Patrick R,Crum B,Coles J

    更新日期:1969-10-01 00:00:00

  • A long noncoding RNA connects c-Myc to tumor metabolism.

    abstract::Long noncoding RNAs (lncRNAs) have been implicated in a variety of physiological and pathological processes, including cancer. In prostate cancer, prostate cancer gene expression marker 1 (PCGEM1) is an androgen-induced prostate-specific lncRNA whose overexpression is highly associated with prostate tumors. PCGEM1's t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1415669112

    authors: Hung CL,Wang LY,Yu YL,Chen HW,Srivastava S,Petrovics G,Kung HJ

    更新日期:2014-12-30 00:00:00

  • A theory of measuring, electing, and ranking.

    abstract::The impossibility theorems that abound in the theory of social choice show that there can be no satisfactory method for electing and ranking in the context of the traditional, 700-year-old model. A more realistic model, whose antecedents may be traced to Laplace and Galton, leads to a new theory that avoids all imposs...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0702634104

    authors: Balinski M,Laraki R

    更新日期:2007-05-22 00:00:00

  • Social interactions, information use, and the evolution of collective migration.

    abstract::Migration of organisms (or cells) is typically an adaptive response to spatiotemporal variation in resources that requires individuals to detect and respond to long-range and noisy environmental gradients. Many organisms, from wildebeest to bacteria, migrate en masse in a process that can involve a vast number of indi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1006874107

    authors: Guttal V,Couzin ID

    更新日期:2010-09-14 00:00:00

  • The virulence factor AvrXa7 of Xanthomonas oryzae pv. oryzae is a type III secretion pathway-dependent nuclear-localized double-stranded DNA-binding protein.

    abstract::AvrXa7 is a member of the avrBs3 avirulence gene family, which encodes proteins targeted to plant cells by a type III secretion apparatus. AvrXa7, the product of avrXa7, is also a virulence factor in strain PXO86 of Xanthomonas oryzae pv. oryzae. Avirulence and virulence specificities are associated with the central r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.170286897

    authors: Yang B,Zhu W,Johnson LB,White FF

    更新日期:2000-08-15 00:00:00

  • An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state.

    abstract::Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs....

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1212811109

    authors: Polytarchou C,Iliopoulos D,Struhl K

    更新日期:2012-09-04 00:00:00

  • Dry granular flows can generate surface features resembling those seen in Martian gullies.

    abstract::Over the past decade or more, contradictory evidence of Martian climate, indicating that surface temperatures seldom if ever approach the melting point of water at midlatitudes, and geomorphic features, consistent with liquid flows at these same latitudes, have proven difficult to reconcile. In this article, we demons...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0308251101

    authors: Shinbrot T,Duong NH,Kwan L,Alvarez MM

    更新日期:2004-06-08 00:00:00

  • Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis.

    abstract::Pbx-regulating protein-1 (Prep1) is a tumor suppressor, whereas myeloid ecotropic viral integration site-1 (Meis1) is an oncogene. We show that, to perform these activities in mouse embryonic fibroblasts, both proteins competitively heterodimerize with pre-B-cell leukemia homeobox-1 (Pbx1). Meis1 alone transforms Prep...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1321200111

    authors: Dardaei L,Longobardi E,Blasi F

    更新日期:2014-03-11 00:00:00

  • Specific interaction of mutant p53 with regions of matrix attachment region DNA elements (MARs) with a high potential for base-unpairing.

    abstract::Mutant, but not wild-type p53 binds with high affinity to a variety of MAR-DNA elements (MARs), suggesting that MAR-binding of mutant p53 relates to the dominant-oncogenic activities proposed for mutant p53. MARs recognized by mutant p53 share AT richness and contain variations of an AATATATTT "DNA-unwinding motif," w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.23.13681

    authors: Will K,Warnecke G,Wiesmüller L,Deppert W

    更新日期:1998-11-10 00:00:00