scholarly journals Biosynthesis and secretion of the microbial sulfated peptide RaxX and binding to the rice XA21 immune receptor

2019 ◽  
Vol 116 (17) ◽  
pp. 8525-8534 ◽  
Author(s):  
Dee Dee Luu ◽  
Anna Joe ◽  
Yan Chen ◽  
Katarzyna Parys ◽  
Ofir Bahar ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Process ◽  
Peptide Hormone ◽  
Xanthomonas Oryzae ◽  
Targeted Proteomics ◽  
Mature Peptide ◽  
Immune Receptor ◽  
High Affinity ◽  
Precursor Peptide ◽  
Modified Peptides

The rice immune receptor XA21 is activated by the sulfated microbial peptide required for activation of XA21-mediated immunity X (RaxX) produced byXanthomonas oryzaepv.oryzae(Xoo). Mutational studies and targeted proteomics revealed that the RaxX precursor peptide (proRaxX) is processed and secreted by the protease/transporter RaxB, the function of which can be partially fulfilled by a noncognate peptidase-containing transporter component B (PctB). proRaxX is cleaved at a Gly–Gly motif, yielding a mature peptide that retains the necessary elements for RaxX function as an immunogen and host peptide hormone mimic. These results indicate that RaxX is a prokaryotic member of a previously unclassified and understudied group of eukaryotic tyrosine sulfated ribosomally synthesized, posttranslationally modified peptides (RiPPs). We further demonstrate that sulfated RaxX directly binds XA21 with high affinity. This work reveals a complete, previously uncharacterized biological process: bacterial RiPP biosynthesis, secretion, binding to a eukaryotic receptor, and triggering of a robust host immune response.

scholarly journals Sulfated RaxX, which represents an unclassified group of ribosomally synthesized post-translationally modified peptides, binds a host immune receptor

2018 ◽  
Author(s):  
Dee Dee Luu ◽  
Anna Joe ◽  
Yan Chen ◽  
Katarzyna Parys ◽  
Ofir Bahar ◽  
...  
Keyword(s):  
Immune Response ◽  
Biological Process ◽  
Peptide Hormone ◽  
Xanthomonas Oryzae ◽  
Targeted Proteomics ◽  
Mature Peptide ◽  
Immune Receptor ◽  
High Affinity ◽  
Founding Member ◽  
Modified Peptides

ABSTRACTThe rice immune receptor XA21 is activated by the sulfated microbial peptide RaxX (required foractivation ofXA21-mediated immunityX) produced byXanthomonas oryzaepv.oryzae(Xoo). Mutational studies and targeted proteomics revealed that RaxX is processed and secreted by the protease/transporter RaxB, whose function can be partially fulfilled by a noncognatepeptidase-containing transporterB(PctB). RaxX is cleaved at a Gly-Gly motif, yielding a mature peptide that retains the necessary elements for RaxX function as an immunogen and host peptide hormone mimic. These results indicate that RaxX is a founding member of a previously unclassified and understudied group of tyrosine sulfated RiPPs (ribosomally synthesized,post-translationally modifiedpeptides). We further demonstrate that sulfated RaxX directly binds XA21 with high affinity. This work reveals a complete, previously uncharacterized biological process: bacterial RiPP biosynthesis, secretion, binding to a eukaryotic receptor and triggering of a robust host immune response.

scholarly journals Variation and inheritance of the Xanthomonas gene cluster required for activation of XA21-mediated immunity

2017 ◽  
Author(s):  
Furong Liu ◽  
Megan McDonald ◽  
Benjamin Schwessinger ◽  
Anna Joe ◽  
Rory Pruitt ◽  
...  
Keyword(s):  
Immune Response ◽  
Gene Cluster ◽  
Peptide Hormone ◽  
Secretion System ◽  
Functional Similarity ◽  
Xanthomonas Oryzae ◽  
Lateral Transfer ◽  
Missense Mutations ◽  
Phylogenetic Distribution ◽  
Hormone Activity

SummaryThe rice XA21-mediated immune response is activated upon recognition of the RaxX peptide produced by the bacterium Xanthomonas oryzae pv. oryzae (Xoo). The 60 residue RaxX precursor is posttranslationally modified to form a sulfated tyrosine peptide that shares sequence and functional similarity with the plant sulfated tyrosine (PSY) peptide hormones. The five kb raxX-raxSTAB gene cluster of Xoo encodes RaxX, the RaxST tyrosylprotein sulfotransferase, and the RaxA and RaxB components of a predicted type one secretion system. The identified the complete raxX-raxSTAB gene cluster is present only in Xanthomonas spp., in five distinct lineages in addition to X. oryzae. The phylogenetic distribution of the raxX-raxSTAB gene cluster is consistent with the occurrence of multiple lateral transfer events during Xanthomonas speciation. RaxX variants representing each of the five lineages, and three Xoo RaxX variants, fail to activate the XA21-mediated immune response yet retain peptide hormone activity. These RaxX variants contain a restricted set of missense mutations, consistent with the hypothesis that selection acts to maintain peptide hormone-like function. These observations are also consistent with the hypothesis that the XA21 receptor evolved specifically to recognize Xoo RaxX.

High level expression of the Drosophila Toll receptor ectodomain and crystallization of its complex with the morphogen Spätzle

2013 ◽  
Vol 394 (8) ◽  
pp. 1091-1096 ◽  
Author(s):  
Marco Stelter ◽  
Uwe Fandrich ◽  
Kati Franzke ◽  
Angelika Schierhorn ◽  
Constanze Breithaupt ◽  
...  
Keyword(s):  
Immune Response ◽  
High Level Expression ◽  
Receptor Ligand ◽  
High Affinity ◽  
Cystine Knot ◽  
Toll Receptor ◽  
Cystine Knot Protein ◽  
High Yields ◽  
High Level ◽  
Affinity Interaction

Abstract Drosophila Toll receptors are involved in embryonic development and in the immune response of adult flies. In both processes, the Toll receptor ligand is the NGF-like cystine knot protein Spätzle. Here we present the expression of Toll receptor ectodomain in Schneider cells at high yields and demonstrate a high affinity interaction with the refolded and trypsin-processed Spätzle cystine knot domain dimer. Poorly and anisotropically diffracting crystals of the complex could be improved by deglycosylation and dehydration, paving the way for structural analyses of the Toll-Spätzle interaction.

scholarly journals The Structural Basis of Repertoire Shift in an Immune Response to Phosphocholine

2000 ◽  
Vol 191 (12) ◽  
pp. 2101-2112 ◽  
Author(s):  
McKay Brown ◽  
Maria A. Schumacher ◽  
Gregory D. Wiens ◽  
Richard G. Brennan ◽  
Marvin B. Rittenberg
Keyword(s):  
Immune Response ◽  
Light Chain ◽  
Indirect Effects ◽  
Somatic Mutations ◽  
Variable Region ◽  
Primary Response ◽  
Structural Basis ◽  
Antibody Repertoire ◽  
High Affinity

The immune response to phosphocholine (PC)–protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high affinity to PC–protein. The somatically mutated memory hybridoma, M3C65, possesses high affinity for PC–protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine (NPPC). Affinity measurements using related PC–phenyl analogues, including peptides of varying lengths, demonstrate that carrier determinants contribute to binding affinity and that somatic mutations alter this recognition. The crystal structure of an M3C65–NPPC complex at 2.35-Å resolution allows evaluation of the three light chain mutations that confer high-affinity binding to NPPC. Only one of the mutations involves a contact residue, whereas the other two have indirect effects on the shape of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural evidence for the role of carrier determinants in promoting repertoire shift. These two antibodies express unrelated variable region heavy and light chain genes and represent a classic example of the effect of repertoire shift on maturation of the immune response.

CP Poly(A) RNA Binding Immunity via Outside-in Glycosyltransfer with MT of BTRC-Activating L12535 and PIN1 Subnetworks for Cognition in PFC|CD14

2020 ◽  
Author(s):  
Lin Wang ◽  
Qingchun Chen ◽  
Haitao Feng ◽  
Minghu Jiang ◽  
Juxiang Huang ◽  
...  
Keyword(s):  
Immune Response ◽  
Network Inference ◽  
Rna Binding ◽  
Biological Process ◽  
Cellular Component ◽  
Innate Immune ◽  
Molecular Function ◽  
Ubiquitin Protein Ligase ◽  
The Common ◽  
Cluster Of Differentiation

Abstract Background: Ras suppressor protein 1 (L12535) and peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) common molecular and knowledge subnetworks containing microtubule associated protein 1B-MAP1B_1 (upstream) related to cognition by references were identified in human left hemisphere, based on our established significant high expression beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC)-activating downstream Gene (protein) reconstruction network inference (GRNInfer) and Database for Annotation, Visualization and Integrated Discovery (DAVID).Results: Our results show the common molecules exostosin-like glycosyltransferase 2 (EXTL2) interaction with MAP1B_1 both activating TERF1_1 with HSP90AB1 from BTRC-activating downstream GRNInfer database; The common biological process and molecular function of MAP1B_1, TERF1_1 as microtubule (MT) binding; HSP90AB1 as poly(A) RNA binding; BTRC, HSP90AB1, PIN1 as innate immune response from BTRC-activating downstream DAVID database; The common cellular component of EXTL2 at integral component of membrane; MAP1B_1, HSP90AB1, TERF1_1 at cytoplasm (CP); The common tissue distributions of L12535 and PIN1 in Prefrontal Cortex (PFC), PB cluster of differentiation (CD)14+Monocytes.Conclusions: We propose and mutual positively verify CP poly(A) RNA binding immunity via outside-in glycosyltransfer with MT of BTRC-activating L12535 and PIN1 subnetworks for cognition in PFC|CD14.

scholarly journals Conformational rearrangements enable iterative backbone N-methylation in RiPP biosynthesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fredarla S. Miller ◽  
Kathryn K. Crone ◽  
Matthew R. Jensen ◽  
Sudipta Shaw ◽  
William R. Harcombe ◽  
...  
Keyword(s):  
Natural Product ◽  
Biological Membrane ◽  
Shewanella Oneidensis ◽  
Structural Constraints ◽  
Peptide Backbone ◽  
Amide Bonds ◽  
Type Iv ◽  
Precursor Peptide ◽  
Modified Peptides ◽  
Conformational Rearrangements

AbstractPeptide backbone α-N-methylations change the physicochemical properties of amide bonds to provide structural constraints and other favorable characteristics including biological membrane permeability to peptides. Borosin natural product pathways are the only known ribosomally encoded and posttranslationally modified peptides (RiPPs) pathways to incorporate backbone α-N-methylations on translated peptides. Here we report the discovery of type IV borosin natural product pathways (termed ‘split borosins’), featuring an iteratively acting α-N-methyltransferase and separate precursor peptide substrate from the metal-respiring bacterium Shewanella oneidensis. A series of enzyme-precursor complexes reveal multiple conformational states for both α-N-methyltransferase and substrate. Along with mutational and kinetic analyses, our results give rare context into potential strategies for iterative maturation of RiPPs.

scholarly journals Competitive Selection from Single Domain Antibody Libraries Allows Isolation of High-Affinity Antihapten Antibodies That Are Not Favored in the llama Immune Response

2011 ◽  
Vol 83 (18) ◽  
pp. 7213-7220 ◽  
Author(s):  
Sofia Tabares-da Rosa ◽  
Martin Rossotti ◽  
Carmen Carleiza ◽  
Federico Carrión ◽  
Otto Pritsch ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Competitive Selection ◽  
High Affinity ◽  
Domain Antibody ◽  
Antibody Libraries
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