scholarly journals CMD: A Database to Store the Bonding States of Cysteine Motifs with Secondary Structures

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Hamed Bostan ◽  
Naomie Salim ◽  
Zeti Azura Hussein ◽  
Peter Klappa ◽  
Mohd Shahir Shamsir
Keyword(s):  
Secondary Structure ◽  
High Throughput Screening ◽  
Laboratory Data ◽  
Cysteine Residue ◽  
Third Party ◽  
Connectivity Pattern ◽  
Cysteine Residues ◽  
Sequence Motif ◽  
Sequence Motifs ◽  
Cysteine Motifs

Computational approaches to the disulphide bonding state and its connectivity pattern prediction are based on various descriptors. One descriptor is the amino acid sequence motifs flanking the cysteine residue motifs. Despite the existence of disulphide bonding information in many databases and applications, there is no complete reference and motif query available at the moment. Cysteine motif database (CMD) is the first online resource that stores all cysteine residues, their flanking motifs with their secondary structure, and propensity values assignment derived from the laboratory data. We extracted more than 3 million cysteine motifs from PDB and UniProt data, annotated with secondary structure assignment, propensity value assignment, and frequency of occurrence and coefficiency of their bonding status. Removal of redundancies generated 15875 unique flanking motifs that are always bonded and 41577 unique patterns that are always nonbonded. Queries are based on the protein ID, FASTA sequence, sequence motif, and secondary structure individually or in batch format using the provided APIs that allow remote users to query our database via third party software and/or high throughput screening/querying. The CMD offers extensive information about the bonded, free cysteine residues, and their motifs that allows in-depth characterization of the sequence motif composition.

scholarly journals Searching for ncRNAs in eukaryotic genomes: Maximizing biological input with RNAmotif

2004 ◽  
Vol 1 (1) ◽  
pp. 64-79 ◽  
Author(s):  
Lesley J. Collins ◽  
Thomas J. Macke ◽  
David Penny
Keyword(s):  
Secondary Structure ◽  
Rna Binding ◽  
Genomic Sequence ◽  
Biological Information ◽  
Biological Knowledge ◽  
Sequence Motif ◽  
Sequence Motifs ◽  
Ncrna Gene ◽  
Ribonucleoprotein Complexes ◽  
Eukaryotic Genomes

Summary Non-coding RNAs (ncRNAs) contain both characteristic secondary-structure and short sequence motifs. However, “complex” ncRNAs (RNA bound to proteins in ribonucleoprotein complexes) can be hard to identify in genomic sequence data. Programs able to search for ncRNAs were previously limited to ncRNA molecules that either align very well or have highly conserved secondary-structure. The RNAmotif program uses additional information to find ncRNA gene candidates through the design of an appropriate “descriptor” to model sequence motifs, secondary-structure and protein/RNA binding information. This enables searches of those ncRNAs that contain variable secondary-structure and limited sequence motif information. Applying the biologically-based concept of “positive and negative controls” to the RNAmotif search technique, we can now go beyond the testing phase to successfully search real genomes, complete with their background noise and related molecules. Descriptors are designed for two “complex” ncRNAs, the U5snRNA (from the spliceosome) and RNaseP RNA, which successfully uncover these sequences from some eukaryotic genomes. We include explanations about the construction of the input “descriptors” from known biological information, to allow searches for other ncRNAs. RNAmotif maximizes the input of biological knowledge into a search for an ncRNA gene and now allows the investigation of some of the hardest-to-find, yet important, genes in some very interesting eukaryotic organisms.

scholarly journals An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation

2017 ◽  
Author(s):  
Emmanuel Oppong ◽  
Gunter Stier ◽  
Miriam Gaal ◽  
Rebecca Seeger ◽  
Melanie Stoeck ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Amyloid Fibrils ◽  
Intrinsic Property ◽  
Activation Function ◽  
Cysteine Residue ◽  
Sequence Motif ◽  
Sequence Motifs ◽  
Conserved Sequence ◽  
Amino Terminal ◽  
Intrinsically Disordered

The human androgen receptor (AR) is a ligand inducible transcription factor harboring an amino terminal domain (AR-NTD) hosting the ligand independent activation function. AR-NTD is intrinsically disordered and display aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence of 22 residues. The length of the polyQ sequence, as well as the presence of adjacent sequence motifs modulate this aggregation property. AR-NTD contains also a conserved sequence motif KELCKAVSVSM that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions of its conserved cysteine residue. As peptide sequences with intrinsic ability to oligomerize are reported to have an impact on the aggregation of polyQ tract, we determined the effect of the KELCKAVSVSM on the polyQ stretch in the context of the AR NTD, using Atomic Force Microscopy (AFM). Here, we present evidence for a crosstalk between the amyloidogenic properties of the KELCKAVSVSM motif and the polyQ stretch at the AR NTD.

scholarly journals The Carboxy-Terminal Domain of Glycoprotein N of Human Cytomegalovirus Is Required for Virion Morphogenesis

2007 ◽  
Vol 81 (10) ◽  
pp. 5212-5224 ◽  
Author(s):  
Michael Mach ◽  
Karolina Osinski ◽  
Barbara Kropff ◽  
Ursula Schloetzer-Schrehardt ◽  
Magdalena Krzyzaniak ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Critical Role ◽  
Point Mutations ◽  
Cysteine Residue ◽  
Cysteine Residues ◽  
Type I ◽  
Terminal Domain ◽  
Carboxy Terminal Domain ◽  
Carboxy Terminal ◽  
Assembly Compartment

ABSTRACT Glycoproteins M and N (gM and gN, respectively) are among the few proteins that are conserved across the herpesvirus family. The function of the complex is largely unknown. Whereas deletion from most alphaherpesviruses has marginal effects on the replication of the respective viruses, both proteins are essential for replication of human cytomegalovirus (HCMV). We have constructed a series of mutants in gN to study the function of this protein. gN of HCMV is a type I glycoprotein containing a short carboxy-terminal domain of 14 amino acids, including two cysteine residues directly adjacent to the predicted transmembrane anchor at positions 125 and 126. Deletion of the entire carboxy-terminal domain as well as substitution with the corresponding region from alpha herpesviruses or mutations of both cysteine residues resulted in a replication-incompetent virus. Recombinant viruses containing point mutations of either cysteine residue could be generated. These viruses were profoundly defective for replication. Complex formation of the mutant gNs with gM and transport of the complex to the viral assembly compartment appeared unaltered compared to the wild type. However, in infected cells, large numbers of capsids accumulated in the cytoplasm that failed to acquire an envelope. Transiently expressed gN was shown to be modified by palmitic acid at both cysteine residues. In summary, our data suggest that the carboxy-terminal domain of gN plays a critical role in secondary envelopment of HCMV and that palmitoylation of gN appears to be essential for function in secondary envelopment of HCMV and virus replication.

Olf-1-binding site: characterization of an olfactory neuron-specific promoter motif

1993 ◽  
Vol 13 (5) ◽  
pp. 3002-3014
Author(s):  
K Kudrycki ◽  
C Stein-Izsak ◽  
C Behn ◽  
M Grillo ◽  
R Akeson ◽  
...  
Keyword(s):  
Nuclear Protein ◽  
Consensus Sequence ◽  
Binding Motif ◽  
Sequence Motif ◽  
Olfactory Neuron ◽  
Sequence Motifs ◽  
Mobility Shift ◽  
Specific Expression ◽  
Mobility Shift Assay

We report characterization of several domains within the 5' flanking region of the olfactory marker protein (OMP) gene that may participate in regulating transcription of this and other olfactory neuron-specific genes. Analysis by electrophoretic mobility shift assay and DNase I footprinting identifies two regions that contain a novel sequence motif. Interactions between this motif and nuclear proteins were detected only with nuclear protein extracts derived from olfactory neuroepithelium, and this activity is more abundant in olfactory epithelium enriched in immature neurons. We have designated a factor(s) involved in this binding as Olf-1. The Olf-1-binding motif consensus sequence was defined as TCCCC(A/T)NGGAG. Studies with transgenic mice indicate that a 0.3-kb fragment of the OMP gene containing one Olf-1 motif is sufficient for olfactory tissue-specific expression of the reporter gene. Some of the other identified sequence motifs also interact specifically with olfactory nuclear protein extracts. We propose that Olf-1 is a novel, olfactory neuron-specific trans-acting factor involved in the cell-specific expression of OMP.

scholarly journals Identification of persulfide-binding and disulfide-forming cysteine residues in the NifS-like domain of the molybdenum cofactor sulfurase ABA3 by cysteine-scanning mutagenesis

2012 ◽  
Vol 441 (3) ◽  
pp. 823-839 ◽  
Author(s):  
Markus Lehrke ◽  
Steffen Rump ◽  
Torsten Heidenreich ◽  
Josef Wissing ◽  
Ralf R. Mendel ◽  
...  
Keyword(s):  
Structural Model ◽  
Bond Distance ◽  
Aldehyde Oxidase ◽  
Disulfide Bridge ◽  
Cysteine Residue ◽  
Molybdenum Cofactor ◽  
Cysteine Residues ◽  
Xanthine Oxidoreductase ◽  
Cysteine Scanning Mutagenesis ◽  
Molybdenum Cofactor Sulfurase

The Moco (molybdenum cofactor) sulfurase ABA3 from Arabidopsis thaliana catalyses the sulfuration of the Moco of aldehyde oxidase and xanthine oxidoreductase, which represents the final activation step of these enzymes. ABA3 consists of an N-terminal NifS-like domain that exhibits L-cysteine desulfurase activity and a C-terminal domain that binds sulfurated Moco. The strictly conserved Cys430 in the NifS-like domain binds a persulfide intermediate, which is abstracted from the substrate L-cysteine and finally needs to be transferred to the Moco of aldehyde oxidase and xanthine oxidoreductase. In addition to Cys430, another eight cysteine residues are located in the NifS-like domain, with two of them being highly conserved among Moco sulfurase proteins and, at the same time, being in close proximity to Cys430. By determination of the number of surface-exposed cysteine residues and the number of persulfide-binding cysteine residues in combination with the sequential substitution of each of the nine cysteine residues, a second persulfide-binding cysteine residue, Cys206, was identified. Furthermore, the active-site Cys430 was found to be located on top of a loop structure, formed by the two flanking residues Cys428 and Cys435, which are likely to form an intramolecular disulfide bridge. These findings are confirmed by a structural model of the NifS-like domain, which indicates that Cys428 and Cys435 are within disulfide bond distance and that a persulfide transfer from Cys430 to Cys206 is indeed possible.

scholarly journals Conserved sequence motifs, alignment, and secondary structure for the third domain of animal 12S rRNA

1996 ◽  
Vol 13 (1) ◽  
pp. 150-169 ◽  
Author(s):  
R. E. Hickson ◽  
C. Simon ◽  
A. Cooper ◽  
G. S. Spicer ◽  
J. Sullivan ◽  
...  
Keyword(s):  
Secondary Structure ◽  
12S Rrna ◽  
Sequence Motifs ◽  
Conserved Sequence ◽  
The Third ◽  
Conserved Sequence Motifs

Modification of a novel x-type high-molecular-weight glutenin subunit gene from Aegilops markgrafii to improve dough strength of wheat flour

2018 ◽  
Vol 69 (9) ◽  
pp. 873
Author(s):  
Xin Ma ◽  
Xuye Du ◽  
Cunyao Bo ◽  
Hongwei Wang ◽  
Anfei Li ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Wheat Flour ◽  
Cysteine Residue ◽  
Site Directed Mutagenesis ◽  
Cysteine Residues ◽  
Dough Strength ◽  
Typical Structure ◽  
Dough Quality

High-molecular-weight glutenin subunits (HMW-GS) in bread wheat are major determinants of dough viscoelastic properties and the end-use quality of wheat flour. Cysteine residues, which form intermolecular disulphide bonds in HMW-GS, could improve the strength of gluten. To our knowledge, the number and position of cysteine residues in HMW-GS are conserved between wheat (Triticum aestivum) and Aegilops markgrafii. In the present study, we modified a gene (1Cx1.1) from Ae. markgrafii for an HMW-GS that possessed the typical structure and conserved number of cysteines. Site-directed mutagenesis was carried out in 1Cx1.1 to investigate how the position of cysteine residues in HMW-GS affects the mixing properties of dough. Six HMW-GS containing an extra cysteine residue were expressed in Escherichia coli, and the proteins were purified at sufficient scale for incorporation into flour to test dough quality. There were large differences in dough property among samples containing different modified subunits. Cysteine substituting in the N-terminal or repetitive-domain of HMW-GS could significantly improve dough quality. The results showed that the strategy was useful for providing genetic resources for gene engineering, and hence could be valuable for improving the processing quality of wheat.

scholarly journals Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

2016 ◽  
Vol 8 (11) ◽  
pp. 3471-3484 ◽  
Author(s):  
Jordon Rahaman ◽  
Jessica Siltberg-Liberles
Keyword(s):  
Secondary Structure ◽  
Structure Prediction ◽  
Secondary Structure Prediction ◽  
Nonstructural Protein ◽  
Intrinsic Disorder ◽  
Sequence Motif ◽  
Protein Families ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Antiviral Targets

Abstract Within the last 15 years, two related coronaviruses (Severe Acute Respiratory Syndrome [SARS]-CoV and Middle East Respiratory Syndrome [MERS]-CoV) expanded their host range to include humans, with increased virulence in their new host. Coronaviruses were recently found to have little intrinsic disorder compared with many other virus families. Because intrinsically disordered regions have been proposed to be important for rewiring interactions between virus and host, we investigated the conservation of intrinsic disorder and secondary structure in coronaviruses in an evolutionary context. We found that regions of intrinsic disorder are rarely conserved among different coronavirus protein families, with the primary exception of the nucleocapsid. Also, secondary structure predictions are only conserved across 50–80% of sites for most protein families, with the implication that 20–50% of sites do not have conserved secondary structure prediction. Furthermore, nonconserved structure sites are significantly less constrained in sequence divergence than either sites conserved in the secondary structure or sites conserved in loop. Avoiding regions symptomatic of conformational flexibility such as disordered sites and sites with nonconserved secondary structure to identify potential broad-specificity antiviral targets, only one sequence motif (five residues or longer) remains from the >10,000 starting sites across all coronaviruses in this study. The identified sequence motif is found within the nonstructural protein (NSP) 12 and constitutes an antiviral target potentially effective against the present day and future coronaviruses. On shorter evolutionary timescales, the SARS and MERS clades have more sequence motifs fulfilling the criteria applied. Interestingly, many motifs map to NSP12 making this a prime target for coronavirus antivirals.

scholarly journals Intra- and Intermolecular Disulfide Bonds of theGP2b Glycoprotein of Equine Arteritis Virus: Relevance forVirus Assembly andInfectivity

2003 ◽  
Vol 77 (24) ◽  
pp. 12996-13004 ◽  
Author(s):  
Roeland Wieringa ◽  
Antoine A. F. de Vries ◽  
Sabine M. Post ◽  
Peter J. M. Rottier
Keyword(s):  
Viral Entry ◽  
Disulfide Bonds ◽  
Rna Virus ◽  
Cysteine Residue ◽  
Envelope Proteins ◽  
Equine Arteritis Virus ◽  
Cysteine Residues ◽  
Virus Infectivity ◽  
Particle Assembly ◽  
Positive Strand Rna

ABSTRACT Equine arteritis virus (EAV) is an enveloped, positive-strand RNA virus belonging to the family Arteriviridae of the order Nidovirales. EAV virions contain six different envelope proteins. The glycoprotein GP5 (previously named GL) and the unglycosylated membrane protein M are the major envelope proteins, while the glycoproteins GP2b (previously named GS), GP3, and GP4 are minor structural proteins. The unglycosylated small hydrophobic envelope protein E is present in virus particles in intermediate molar amounts compared to the other transmembrane proteins. The GP5 and M proteins are both essential for particle assembly. They occur as covalently linked heterodimers that constitute the basic protein matrix of the envelope. The GP2b, GP3, and GP4 proteins occur as a heterotrimeric complex in which disulfide bonds play an important role. The function of this complex has not been established yet, but the available data suggest it to be involved in the viral entry process. Here we investigated the role of the four cysteine residues of the mature GP2b protein in the assembly of the GP2b/GP3/GP4 complex. Open reading frames encoding cysteine-to-serine mutants of the GP2b protein were expressed independently or from a full-length infectious EAV cDNA clone. The results of these experiments support a model in which the cysteine residue at position 102 of GP2b forms an intermolecular cystine bridge with one of the cysteines of the GP4 protein, while the cysteine residues at positions 48 and 137 of GP2b are linked by an intrachain disulfide bond. In this model, another cysteine residue in the GP4 protein is responsible for the covalent association of GP3 with the disulfide-linked GP2b/GP4 heterodimer. In addition, our data highlight the importance of the correct association of the minor EAV envelope glycoproteins for their efficient incorporation into viral particles and for virus infectivity.

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