scholarly journals Leucine-Rich Repeats and Immunoglobulin-Like Domains Protein 1

2020 ◽  
Author(s):  
Keyword(s):  
Leucine Rich Repeats

scholarly journals Nucleotide-Binding Leucine-Rich Repeat Genes CsRSF1 and CsRSF2 Are Positive Modulators in the Cucumis sativus Defense Response to Sphaerotheca fuliginea

2021 ◽  
Vol 22 (8) ◽  
pp. 3986
Author(s):  
Xue Wang ◽  
Qiumin Chen ◽  
Jingnan Huang ◽  
Xiangnan Meng ◽  
Na Cui ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Defense Response ◽  
Nucleotide Binding ◽  
Plant Defense Response ◽  
Sphaerotheca Fuliginea ◽  
Leucine Rich Repeat ◽  
Transcript Levels ◽  
Yield And Quality ◽  
Leucine Rich Repeats ◽  
Exogenous Substances

Cucumber powdery mildew caused by Sphaerotheca fuliginea is a leaf disease that seriously affects cucumber’s yield and quality. This study aimed to report two nucleotide-binding site-leucine-rich repeats (NBS-LRR) genes CsRSF1 and CsRSF2, which participated in regulating the resistance of cucumber to S. fuliginea. The subcellular localization showed that the CsRSF1 protein was localized in the nucleus, cytoplasm, and cell membrane, while the CsRSF2 protein was localized in the cell membrane and cytoplasm. In addition, the transcript levels of CsRSF1 and CsRSF2 were different between resistant and susceptible cultivars after treatment with exogenous substances, such as abscisic acid (ABA), methyl jasmonate (MeJA), salicylic acid (SA), ethephon (ETH), gibberellin (GA) and hydrogen peroxide (H2O2). The expression analysis showed that the transcript levels of CsRSF1 and CsRSF2 were correlated with plant defense response against S. fuliginea. Moreover, the silencing of CsRSF1 and CsRSF2 impaired host resistance to S. fuliginea, but CsRSF1 and CsRSF2 overexpression improved resistance to S. fuliginea in cucumber. These results showed that CsRSF1 and CsRSF2 genes positively contributed to the resistance of cucumber to S. fuliginea. At the same time, CsRSF1 and CsRSF2 genes could also regulate the expression of defense-related genes. The findings of this study might help enhance the resistance of cucumber to S. fuliginea.

scholarly journals LRIG1 is a conserved EGFR regulator involved in melanoma development, survival and treatment resistance

Oncogene ◽  
2021 ◽  
Author(s):  
Ola Billing ◽  
Ylva Holmgren ◽  
Daniel Nosek ◽  
Håkan Hedman ◽  
Oskar Hemmingsson
Keyword(s):  
Growth Factor Receptor ◽  
Braf Inhibitor ◽  
Treatment Resistance ◽  
Negative Regulator ◽  
C Elegans ◽  
Rtk Signaling ◽  
Egfr Expression ◽  
Inhibitor Resistance ◽  
Leucine Rich Repeats

AbstractLeucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a pan-negative regulator of receptor tyrosine kinase (RTK) signaling and a tumor suppressor in several cancers, but its involvement in melanoma is largely unexplored. Here, we aim to determine the role of LRIG1 in melanoma tumorigenesis, RTK signaling, and BRAF inhibitor resistance. We find that LRIG1 is downregulated during early tumorigenesis and that LRIG1 affects activation of the epidermal growth factor receptor (EGFR) in melanoma cells. LRIG1-dependent regulation of EGFR signaling is evolutionary conserved to the roundworm C. elegans, where negative regulation of the EGFR-Ras-Raf pathway by sma-10/LRIG completely depends on presence of the receptor let-23/EGFR. In a cohort of metastatic melanoma patients, we observe an association between LRIG1 and survival in the triple wild-type subtype and in tumors with high EGFR expression. During in vitro development of BRAF inhibitor resistance, LRIG1 expression decreases; and mimics LRIG1 knockout cells for increased EGFR expression. Treating resistant cells with recombinant LRIG1 suppresses AKT activation and proliferation. Together, our results show that sma-10/LRIG is a conserved regulator of RTK signaling, add to our understanding of LRIG1 in melanoma and identifies recombinant LRIG1 as a potential therapeutic against BRAF inhibitor-resistant melanoma.

scholarly journals Conserved charged residues in the leucine-rich repeat domain of the Ran GTPase activating protein are required for Ran binding and GTPase activation

1999 ◽  
Vol 343 (3) ◽  
pp. 653-662 ◽  
Author(s):  
Jörg HABERLAND ◽  
Volker GERKE
Keyword(s):  
Nucleocytoplasmic Transport ◽  
Small Gtpases ◽  
Structural Basis ◽  
Ran Gtpase ◽  
Protein Protein Interaction ◽  
Charged Residues ◽  
Gtpase Activation ◽  
Gtpase Cycle ◽  
Leucine Rich Repeats ◽  
Lrr Domain

GTPase activating proteins (GAPs) for Ran, a Ras-related GTPase participating in nucleocytoplasmic transport, have been identified in different species ranging from yeast to man. All RanGAPs are characterized by a conserved domain consisting of eight leucine-rich repeats (LRRs) interrupted at two positions by so-called separating regions, the latter being unique for RanGAPs within the family of LRR proteins. The cytosolic RanGAP activity is essential for the Ran GTPase cycle which in turn provides directionality in nucleocytoplasmic transport, but the structural basis for the interaction between Ran and its GAP has not been elucidated. In order to gain a better understanding of this interaction we generated a number of mutant RanGAPs carrying amino acid substitutions in the LRR domain and analysed their complex formation with Ran as well as their ability to stimulate the intrinsic GTPase activity of the G protein. We show that conserved charged residues present in the separating regions of the LRR domain are indispensable for efficient Ran binding and GAP activity. These separating regions contain three conserved arginines which could possibly serve as catalytic residues similar to the arginine fingers identified in GAPs for other small GTPases. However, mutations in two of these arginines do not affect the GAP activity and replacement of the third conserved arginine (Arg91 in human RanGAP) severely interferes not only with GAP activity but also with Ran binding. This indicates that RanGAP-stimulated GTP hydrolysis on Ran does not involve a catalytic arginine residue but requires certain charged residues of the LRR domain of the GAP for mediating the protein-protein interaction.

scholarly journals TAP (NXF1) Belongs to a Multigene Family of Putative RNA Export Factors with a Conserved Modular Architecture

2000 ◽  
Vol 20 (23) ◽  
pp. 8996-9008 ◽  
Author(s):  
Andrea Herold ◽  
Mikita Suyama ◽  
João P. Rodrigues ◽  
Isabelle C. Braun ◽  
Ulrike Kutay ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Rna Binding ◽  
Mrna Export ◽  
Modular Architecture ◽  
Export Activity ◽  
Evolutionarily Conserved ◽  
Rna Export ◽  
Higher Eukaryotes ◽  
Leucine Rich Repeats ◽  
Rna Export Factors

ABSTRACT Vertebrate TAP (also called NXF1) and its yeast orthologue, Mex67p, have been implicated in the export of mRNAs from the nucleus. The TAP protein includes a noncanonical RNP-type RNA binding domain, four leucine-rich repeats, an NTF2-like domain that allows heterodimerization with p15 (also called NXT1), and a ubiquitin-associated domain that mediates the interaction with nucleoporins. Here we show that TAP belongs to an evolutionarily conserved family of proteins that has more than one member in higher eukaryotes. Not only the overall domain organization but also residues important for p15 and nucleoporin interaction are conserved in most family members. We characterize two of four human TAP homologues and show that one of them, NXF2, binds RNA, localizes to the nuclear envelope, and exhibits RNA export activity. NXF3, which does not bind RNA or localize to the nuclear rim, has no RNA export activity. Database searches revealed that although only one p15(nxt) gene is present in the Drosophila melanogaster and Caenorhabditis elegans genomes, there is at least one additional p15 homologue (p15-2 [also called NXT2]) encoded by the human genome. Both human p15 homologues bind TAP, NXF2, and NXF3. Together, our results indicate that the TAP-p15 mRNA export pathway has diversified in higher eukaryotes compared to yeast, perhaps reflecting a greater substrate complexity.

scholarly journals Generation of Lamprey Monoclonal Antibodies (Lampribodies) Using the Phage Display System

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 868 ◽  
Author(s):  
Khan M. A. Hassan ◽  
John D. Hansen ◽  
Brantley R. Herrin ◽  
Chris T. Amemiya
Keyword(s):  
Monoclonal Antibodies ◽  
Phage Display ◽  
Genomic Rearrangements ◽  
Filamentous Phage ◽  
Human Cell Lines ◽  
Display System ◽  
Phage Display Libraries ◽  
Humoral Antibodies ◽  
Leucine Rich Repeats ◽  
Lymphocyte Receptors

The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent VLRB antibodies were isolated from sea lamprey larvae after immunization with model antigens. Further, the cloned VLR cDNAs from activated lamprey leukocytes were transfected into human cell lines or yeast to select best binders. Here, we expand on the overall utility of the VLRB technology by introducing it into a filamentous phage display system. We first tested the efficacy of isolating phage into which known VLRB molecules were cloned after a series of dilutions. These experiments showed that targeted VLRB clones could easily be recovered even after extensive dilutions (1 to 109). We further utilized the system to isolate target-specific “lampribodies” from phage display libraries from immunized animals and observed an amplification of binders with relative high affinities by competitive binding. The lampribodies can be individually purified and ostensibly utilized for applications for which conventional monoclonal antibodies are employed.

scholarly journals In silico analyses of CD14 molecule reveals significant evolutionary diversity potentially associated with speciation and variable immune response in mammals

2019 ◽  
Author(s):  
Olanrewaju B Morenikeji ◽  
Bolaji N Thomas
Keyword(s):  
Immune Response ◽  
Complex Disease ◽  
Mammalian Species ◽  
Coding Region ◽  
Protein Protein Interaction ◽  
Species Response ◽  
Gene Coding ◽  
Protein Interactome ◽  
Mutational Hotspots ◽  
Leucine Rich Repeats

Cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein (LBP), forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine rich repeats (LRRs) as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from 1-4. Importantly, we found signal peptides located at mutational hotspots demonstrating this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only 6 were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.

Shrinking of repeating unit length in leucine-rich repeats from double-stranded DNA viruses

2020 ◽  
Author(s):  
Norio Matsushima ◽  
Hiroki Miyashita ◽  
Shinsuke Tamaki ◽  
Robert H. Kretsinger
Keyword(s):  
Unit Length ◽  
Dna Viruses ◽  
Double Stranded Dna ◽  
Leucine Rich Repeats

scholarly journals LRRpredictor—A New LRR Motif Detection Method for Irregular Motifs of Plant NLR Proteins Using an Ensemble of Classifiers

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 286 ◽  
Author(s):  
Eliza C. Martin ◽  
Octavina C. A. Sukarta ◽  
Laurentiu Spiridon ◽  
Laurentiu G. Grigore ◽  
Vlad Constantinescu ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Structural Data ◽  
Innate Immune ◽  
Protein Protein Interactions ◽  
Ensemble Of Classifiers ◽  
Immune Receptor ◽  
Motif Detection ◽  
Protein Architecture ◽  
Recognition Specificity ◽  
Leucine Rich Repeats

Leucine-rich-repeats (LRRs) belong to an archaic procaryal protein architecture that is widely involved in protein–protein interactions. In eukaryotes, LRR domains developed into key recognition modules in many innate immune receptor classes. Due to the high sequence variability imposed by recognition specificity, precise repeat delineation is often difficult especially in plant NOD-like Receptors (NLRs) notorious for showing far larger irregularities. To address this problem, we introduce here LRRpredictor, a method based on an ensemble of estimators designed to better identify LRR motifs in general but particularly adapted for handling more irregular LRR environments, thus allowing to compensate for the scarcity of structural data on NLR proteins. The extrapolation capacity tested on a set of annotated LRR domains from six immune receptor classes shows the ability of LRRpredictor to recover all previously defined specific motif consensuses and to extend the LRR motif coverage over annotated LRR domains. This analysis confirms the increased variability of LRR motifs in plant and vertebrate NLRs when compared to extracellular receptors, consistent with previous studies. Hence, LRRpredictor is able to provide novel insights into the diversification of LRR domains and a robust support for structure-informed analyses of LRRs in immune receptor functioning.

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