Leucine Rich Repeat Proteins: Sequences, Mutations, Structures and Diseases

2019 ◽  
Vol 26 (2) ◽  
pp. 108-131 ◽  
Author(s):  
Norio Matsushima ◽  
Shintaro Takatsuka ◽  
Hiroki Miyashita ◽  
Robert H. Kretsinger
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Missense Mutations ◽  
Hydrophobic Core ◽  
Leucine Rich Repeat ◽  
Loss Of Function ◽  
Protein Ligand Interactions ◽  
Repeat Proteins ◽  
Genes Encoding ◽  
Ligand Interactions

Mutations in the genes encoding Leucine Rich Repeat (LRR) containing proteins are associated with over sixty human diseases; these include high myopia, mitochondrial encephalomyopathy, and Crohn’s disease. These mutations occur frequently within the LRR domains and within the regions that shield the hydrophobic core of the LRR domain. The amino acid sequences of fifty-five LRR proteins have been published. They include Nod-Like Receptors (NLRs) such as NLRP1, NLRP3, NLRP14, and Nod-2, Small Leucine Rich Repeat Proteoglycans (SLRPs) such as keratocan, lumican, fibromodulin, PRELP, biglycan, and nyctalopin, and F-box/LRR-repeat proteins such as FBXL2, FBXL4, and FBXL12. For example, 363 missense mutations have been identified. Replacement of arginine, proline, or cysteine by another amino acid, or the reverse, is frequently observed. The diverse effects of the mutations are discussed based on the known structures of LRR proteins. These mutations influence protein folding, aggregation, oligomerization, stability, protein-ligand interactions, disulfide bond formation, and glycosylation. Most of the mutations cause loss of function and a few, gain of function.

scholarly journals Novel Few-shots Learning Neural Network for Predicting Carbohydrate-active Enzyme (CAZyme) Affinity Towards Fructo-oligosaccharides

2020 ◽  
Author(s):  
Shaoxun Liu ◽  
Yi Kou ◽  
Lin Chen
Keyword(s):  
Neural Network ◽  
Amino Acid ◽  
Binding Affinity ◽  
Amino Acid Sequences ◽  
Active Enzyme ◽  
Binding Interaction ◽  
Carbohydrate Active Enzyme ◽  
Protein Ligand Interactions ◽  
Enzyme Substrate ◽  
Ligand Interactions

Abstract Background: The enzymatic activity of the microbiome toward carbohydrates in the human digestive system is of enormous health significance (Zou, Y., et al., 2019; Pinard, D., et al., 2015). Predicting how carbohydrates through food intake may affect the distribution and balance of gut microbiota remains a major challenge. Understanding the enzyme-substrate specificity relationship of the carbohydrate-active enzyme (CAZyme) encoded by the vast gut microbiome will be an important step to address this question. In this study, we seek to establish an in-silico approach to studying the enzyme-substrate binding interaction. Results: We focused on the key carbohydrate-active enzyme (CAZyme) and established a novel Poisson noise-based few-shots learning neural network (pFSLNN) for predicting the binding affinity of indigestible carbohydrates. This approach achieved higher accuracy than other classic FSLNNs, and we have also formulated new algorithms for feature generation using only a few amino acid sequences. Sliding bin regression is integrated with mRMR for feature selection. Conclusion: The resulting pFSLNN is an efficient model to predict the binding affinity between CAZyme and common oligosaccharides. This model can be potentially applied to binding affinity prediction of other protein-ligand interactions based on limited amino acid sequences.

Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum

1991 ◽  
Vol 11 (2) ◽  
pp. 963-971
Author(s):  
B Fenton ◽  
J T Clark ◽  
C M Khan ◽  
J V Robinson ◽  
D Walliker ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Surface Antigen ◽  
Dna Sequences ◽  
Amino Acid Sequences ◽  
Merozoite Surface Antigen ◽  
Parasite Plasmodium ◽  
Genes Encoding ◽  
Parasite Plasmodium Falciparum ◽  
Group B

Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is being considered for the development of a malaria vaccine. The antigen is polymorphic, and specific monoclonal antibodies differentiate five serological variants of MSA-2 among 25 parasite isolates. The variants are grouped into two major serogroups, A and B. Genes encoding two different variants from serogroup A have been sequenced, and their DNA together with deduced amino acid sequences were compared with sequences encoded by other alleles. The comparison shows that the serological classification reflects differences in DNA sequences and deduced primary structure of MSA-2 variants and serogroups. Thus, the overall homologies of DNA and amino acid sequences are over 95% among variants in the same serogroup. In contrast, similarities between the group A variants and a group B variant are only 70 and 64% for DNA and amino acid sequences, respectively. We propose that the MSA-2 protein is encoded by two highly divergent groups of alleles, with limited additional polymorphism displayed within each group.

scholarly journals A Budding Yeast Model for Human Disease Mutations in the EXOSC2 Cap Subunit of the RNA Exosome

2020 ◽  
Author(s):  
Maria C. Sterrett ◽  
Liz Enyenihi ◽  
Sara W. Leung ◽  
Laurie Hess ◽  
Sarah E. Strassler ◽  
...  
Keyword(s):  
Amino Acid ◽  
Budding Yeast ◽  
Amino Acid Substitutions ◽  
Missense Mutations ◽  
Subunit Gene ◽  
Rna Targets ◽  
Genes Encoding ◽  
Rna Exosome ◽  
Transcriptomic Changes

AbstractRNA exosomopathies, a growing family of tissue-specific diseases, are linked to missense mutations in genes encoding the structural subunits of the conserved 10-subunit exoribonuclease complex, the RNA exosome. Such mutations in the cap subunit gene EXOSC2 cause the novel syndrome SHRF (Short stature, Hearing loss, Retinitis pigmentosa and distinctive Facies). In contrast, exosomopathy mutations in the cap subunit gene EXOSC3 cause pontocerebellar hypoplasia type 1b (PCH1b). Though having strikingly different disease pathologies, EXOSC2 and EXOSC3 exosomopathy mutations result in amino acid substitutions in similar, conserved domains of the cap subunits, suggesting that these exosomopathy mutations have distinct consequences for RNA exosome function. We generated the first in vivo model of the SHRF pathogenic amino acid substitutions using budding yeast by introducing the EXOSC2 mutations in the orthologous S. cerevisiae gene RRP4. The resulting rrp4 mutant cells have defects in cell growth and RNA exosome function. We detect significant transcriptomic changes in both coding and non-coding RNAs in the rrp4 variant, rrp4-G226D, which models EXOSC2 p.Gly198Asp. Comparing this rrp4-G226D mutant to the previously studied S. cerevisiae model of EXOSC3 PCH1b mutation, rrp40-W195R, reveals that these mutants have disparate effects on certain RNA targets, providing the first evidence for different mechanistic consequences of these exosomopathy mutations. Congruently, we detect specific negative genetic interactions between RNA exosome cofactor mutants and rrp4-G226D but not rrp40-W195R. These data provide insight into how SHRF mutations could alter the function of the RNA exosome and allow the first direct comparison of exosomopathy mutations that cause distinct pathologies.

scholarly journals The Tomato Cf-2 Disease Resistance Locus Comprises Two Functional Genes Encoding Leucine-Rich Repeat Proteins

Cell ◽  
1996 ◽  
Vol 84 (3) ◽  
pp. 451-459 ◽  
Author(s):  
Mark S Dixon ◽  
David A Jones ◽  
James S Keddie ◽  
Colwyn M Thomas ◽  
Kate Harrison ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Functional Genes ◽  
Resistance Locus ◽  
Leucine Rich Repeat ◽  
Repeat Proteins ◽  
Genes Encoding

scholarly journals Prediction of Protein–Ligand Interaction Based on the Positional Similarity Scores Derived from Amino Acid Sequences

2019 ◽  
Vol 21 (1) ◽  
pp. 24 ◽  
Author(s):  
Dmitry Karasev ◽  
Boris Sobolev ◽  
Alexey Lagunin ◽  
Dmitry Filimonov ◽  
Vladimir Poroikov
Keyword(s):  
Prediction Accuracy ◽  
Sequence Similarity ◽  
Amino Acid Sequences ◽  
Protein Families ◽  
Pairwise Sequence Alignment ◽  
Ligand Interaction ◽  
Protein Ligand Interactions ◽  
General Chemical ◽  
Local Sequence ◽  
Ligand Interactions

The affinity of different drug-like ligands to multiple protein targets reflects general chemical–biological interactions. Computational methods estimating such interactions analyze the available information about the structure of the targets, ligands, or both. Prediction of protein–ligand interactions based on pairwise sequence alignment provides reasonable accuracy if the ligands’ specificity well coincides with the phylogenic taxonomy of the proteins. Methods using multiple alignment require an accurate match of functionally significant residues. Such conditions may not be met in the case of diverged protein families. To overcome these limitations, we propose an approach based on the analysis of local sequence similarity within the set of analyzed proteins. The positional scores, calculated by sequence fragment comparisons, are used as input data for the Bayesian classifier. Our approach provides a prediction accuracy comparable or exceeding those of other methods. It was demonstrated on the popular Gold Standard test sets, presenting different sequence heterogeneity and varying from the group, including different protein families to the more specific groups. A reasonable prediction accuracy was also found for protein kinases, displaying weak relationships between sequence phylogeny and inhibitor specificity. Thus, our method can be applied to the broad area of protein–ligand interactions.

scholarly journals Genes for low-molecular-weight heat shock proteins of soybeans: sequence analysis of a multigene family.

1985 ◽  
Vol 5 (12) ◽  
pp. 3417-3428 ◽  
Author(s):  
R T Nagao ◽  
E Czarnecka ◽  
W B Gurley ◽  
F Schöffl ◽  
J L Key
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Heat Shock ◽  
Dna Sequences ◽  
Regulatory Element ◽  
Amino Acid Sequences ◽  
Striking Similarity ◽  
Low Molecular Weight ◽  
Genes Encoding ◽  
Flanking Regions

Soybeans, Glycine max, synthesize a family of low-molecular-weight heat shock (HS) proteins in response to HS. The DNA sequences of two genes encoding 17.5- and 17.6-kilodalton HS proteins were determined. Nuclease S1 mapping of the corresponding mRNA indicated multiple start termini at the 5' end and multiple stop termini at the 3' end. These two genes were compared with two other soybean HS genes of similar size. A comparison among the 5' flanking regions encompassing the presumptive HS promoter of the soybean HS-protein genes demonstrated this region to be extremely homologous. Analysis of the DNA sequences in the 5' flanking regions of the soybean genes with the corresponding regions of Drosophila melanogaster HS-protein genes revealed striking similarity between plants and animals in the presumptive promoter structure of thermoinducible genes. Sequences related to the Drosophila HS consensus regulatory element were found 57 to 62 base pairs 5' to the start of transcription in addition to secondary HS consensus elements located further upstream. Comparative analysis of the deduced amino acid sequences of four soybean HS proteins illustrated that these proteins were greater than 90% homologous. Comparison of the amino acid sequence for soybean HS proteins with other organisms showed much lower homology (less than 20%). Hydropathy profiles for Drosophila, Xenopus, Caenorhabditis elegans, and G. max HS proteins showed a similarity of major hydrophilic and hydrophobic regions, which suggests conservation of functional domains for these proteins among widely dispersed organisms.

scholarly journals The variable subunit associated with protein phosphatase 2A0 defines a novel multimember family of regulatory subunits

1996 ◽  
Vol 317 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Stanislaw ZOLNIEROWICZ ◽  
Christine VAN HOOF ◽  
Nataša ANDJELKOVIĆ ◽  
Peter CRON ◽  
Ilse STEVENS ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Phosphatase ◽  
Amino Acid Sequences ◽  
Regulatory Subunits ◽  
Consensus Sequences ◽  
Reverse Transcription Pcr ◽  
Genes Encoding ◽  
Phosphatase 2A ◽  
Molecular Masses ◽  
Specific Mrnas

Two protein phosphatase 2A (PP2A) holoenzymes were isolated from rabbit skeletal muscle containing, in addition to the catalytic and PR65 regulatory subunits, proteins of apparent molecular masses of 61 and 56 kDa respectively. Both holoenzymes displayed low basal phosphorylase phosphatase activity, which could be stimulated by protamine to an extent similar to that of previously characterized PP2A holoenzymes. Protein microsequencing of tryptic peptides derived from the 61 kDa protein, termed PR61, yielded 117 residues of amino acid sequence. Molecular cloning by enrichment of specific mRNAs, followed by reverse transcription–PCR and cDNA library screening, revealed that this protein exists in multiple isoforms encoded by at least three genes, one of which gives rise to several splicing variants. Comparisons of these sequences with the available databases identified one more human gene and predicted another based on a rabbit cDNA-derived sequence, thus bringing the number of genes encoding PR61 family members to five. Peptide sequences derived from PR61 corresponded to the deduced amino acid sequences of either α or β isoforms, indicating that the purified PP2A preparation was a mixture of at least two trimers. In contrast, the 56 kDa subunit (termed PR56) seems to correspond to the ϵ isoform of PR61. Several regulatory subunits of PP2A belonging to the PR61 family contain consensus sequences for nuclear localization and might therefore target PP2A to nuclear substrates.

scholarly journals Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum.

1991 ◽  
Vol 11 (2) ◽  
pp. 963-971 ◽  
Author(s):  
B Fenton ◽  
J T Clark ◽  
C M Khan ◽  
J V Robinson ◽  
D Walliker ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Amino Acid ◽  
Surface Antigen ◽  
Dna Sequences ◽  
Amino Acid Sequences ◽  
Merozoite Surface Antigen ◽  
Parasite Plasmodium ◽  
Genes Encoding ◽  
Parasite Plasmodium Falciparum ◽  
Group B

Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is being considered for the development of a malaria vaccine. The antigen is polymorphic, and specific monoclonal antibodies differentiate five serological variants of MSA-2 among 25 parasite isolates. The variants are grouped into two major serogroups, A and B. Genes encoding two different variants from serogroup A have been sequenced, and their DNA together with deduced amino acid sequences were compared with sequences encoded by other alleles. The comparison shows that the serological classification reflects differences in DNA sequences and deduced primary structure of MSA-2 variants and serogroups. Thus, the overall homologies of DNA and amino acid sequences are over 95% among variants in the same serogroup. In contrast, similarities between the group A variants and a group B variant are only 70 and 64% for DNA and amino acid sequences, respectively. We propose that the MSA-2 protein is encoded by two highly divergent groups of alleles, with limited additional polymorphism displayed within each group.

scholarly journals Characterization of Novel Carbazole Catabolism Genes from Gram-Positive Carbazole Degrader Nocardioides aromaticivorans IC177

2006 ◽  
Vol 72 (5) ◽  
pp. 3321-3329 ◽  
Author(s):  
Kengo Inoue ◽  
Hiroshi Habe ◽  
Hisakazu Yamane ◽  
Hideaki Nojiri
Keyword(s):  
Amino Acid ◽  
Gene Clusters ◽  
Amino Acid Sequences ◽  
Open Reading Frames ◽  
Class Iii ◽  
Rt Pcr ◽  
Gram Positive ◽  
Mononuclear Iron ◽  
Reverse Transcription Pcr ◽  
Genes Encoding

ABSTRACT Nocardioides aromaticivorans IC177 is a gram-positive carbazole degrader. The genes encoding carbazole degradation (car genes) were cloned into a cosmid clone and sequenced partially to reveal 19 open reading frames. The car genes were clustered into the carAaCBaBbAcAd and carDFE gene clusters, encoding the enzymes responsible for the degradation of carbazole to anthranilate and 2-hydroxypenta-2,4-dienoate and of 2-hydroxypenta-2,4-dienoate to pyruvic acid and acetyl coenzyme A, respectively. The conserved amino acid motifs proposed to bind the Rieske-type [2Fe-2S] cluster and mononuclear iron, the Rieske-type [2Fe-2S] cluster, and flavin adenine dinucleotide were found in the deduced amino acid sequences of carAa, carAc, and carAd, respectively, which showed similarities with CarAa from Sphingomonas sp. strain KA1 (49% identity), CarAc from Pseudomonas resinovorans CA10 (31% identity), and AhdA4 from Sphingomonas sp. strain P2 (37% identity), respectively. Escherichia coli cells expressing CarAaAcAd exhibited major carbazole 1,9a-dioxygenase (CARDO) activity. These data showed that the IC177 CARDO is classified into class IIB, while gram-negative CARDOs are classified into class III or IIA, indicating that the respective CARDOs have diverse types of electron transfer components and high similarities of the terminal oxygenase. Reverse transcription-PCR (RT-PCR) experiments showed that the carAaCBaBbAcAd and carDFE gene clusters are operonic. The results of quantitative RT-PCR experiments indicated that transcription of both operons is induced by carbazole or its metabolite, whereas anthranilate is not an inducer. Biotransformation analysis showed that the IC177 CARDO exhibits significant activities for naphthalene, carbazole, and dibenzo-p-dioxin but less activity for dibenzofuran and biphenyl.

Nucleotide and deduced amino acid sequences of genes encoding the structural and nonstructural NS1 proteins of a dengue-2 virus isolated in China

Virus Genes ◽  
1994 ◽  
Vol 8 (1) ◽  
pp. 71-74 ◽  
Author(s):  
Pei-Ying Yang ◽  
Ingrid Kautner ◽  
Chong-Lek Koh ◽  
Sai-Kit Lam
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequences ◽  
Genes Encoding
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