Nitric oxide-mediated S-nitrosylation of IAA17 protein in intrinsically disordered region represses auxin signaling

The phytohormone auxin plays crucial roles in nearly every aspect of plant growth and development.Auxin signaling is activated through the phytohormone-induced proteasomal degradation of the Auxin/INDOLE-3-ACETIC ACID(Aux/IAA)family of transcriptional repressors.Notably,many auxin-modulated physiological processes are also regulated by nitric oxide(NO)that executes its biological effects predominantly through protein S-nitrosylation at specific cysteine residues.However,little is known about the molecular mechanisms in regulating the interactive NO and auxin networks.Here,we show that NO represses auxin signaling by inhibiting IAA17 protein degradation.NO induces the S-nitrosylation of Cys-70 located in the intrinsically disordered region of IAA17,which inhibits the TIR1-IAA17 interaction and consequently the proteasomal degradation of IAA17.The accumulation of a higher level of IAA17 attenuates auxin response.Moreover,an IAA17^(C70W)nitrosomimetic mutation renders the accumulation of a higher level of the mutated protein,thereby causing partial resistance to auxin and defective lateral root development.Taken together,these results suggest that S-nitrosylation of IAA17 at Cys-70 inhibits its interaction with TIR1,thereby negatively regulating auxin signaling.This study provides unique molecular insights into the redox-based auxin signaling in regulating plant growth and development.

Homepeptide Repeats:Implications for Protein Structure,Function and Evolution

Analysis of protein sequences from Mycobacterium tuberculosis H37Rv （Mtb H37Rv） was performed to identify homopeptide repeat- containing proteins （HRCPs）. Functional annotation of the HRCPs showed that they are preferentially involved in cellular metabolism. Furthermore, these homopeptide repeats might play some specific roles in protein-protein interaction. Repeat length differences among Bacteria, Archaea and Eukaryotes were calculated in order to identify the conservation of the repeats in these divergent kingdoms. From the results, it was evident that these repeats have a higher degree of conservation in Bacteria and Archaea than in Eukaryotes. In addi- tion, there seems to be a direct correlation between the repeat length difference and the degree of divergence between the species. Our study supports the hypothesis that the presence of homopeptide repeats influences the rate of evolution of the protein sequences in which they are embedded. Thus, homopeptide repeat may have structural, functional and evolutionary implications on proteins.

Computational Analysis of Position-dependent Disorder Content in DisProt Database

A bioinformatics analysis of disorder content of proteins from the DisProt database has been performed with respect to position of dis- ordered residues. Each protein chain was divided into three parts： N- and C- terminal parts with each containing 30 amino acid （AA） residues and the middle region containing the remaining AA residues. The results show that in terminal parts, the percentage of disor- dered AA residues is higher than that of all AA residues （17% of disordered AA residues and 11% of all）. We analyzed the percentage of disorder for each of 20 AA residues in the three parts of proteins with respect to their hydropathy and molecular weight. For each AA, the percentage of disorder in the middle part is lower than that in terminal parts which is comparable at the two termini. A new scale of AAs has been introduced according to their disorder content in the middle part of proteins： CIFWMLYHRNVTAGQDSKEP. All big hydrophobic AAs are less frequently disordered, while almost all small hydrophilic AAs are more frequently disordered. The results obtained may be useful for construction and improving predictors for protein disorder.

Local synchronization and amplitude of the fluctuation of spontaneous brain activity in attention-deficit/hyperactivity disorder:a resting-state fMRI study

Regional homogeneity（ReHo）and the amplitude of low-frequency fluctuation（ALFF）are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging（RS-fMRI）data.Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder（ADHD）remains unknown.In this study,we applied ReHo and ALFF to 23 medication-na ve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis.Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD.We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipitocerebellar circuitry,while the ALFF method showed a difference only in the right occipital area.When a larger smoothing kernel and a more lenient threshold were used for ALFF,more overlapped regions were found between ALFF and ReHo,and ALFF even found some new regions with group differences.The ADHD symptom scores were correlated with the ReHo values in the right cerebellum,dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group,while no correlation was detected between ALFF and ADHD symptoms.In conclusion,ReHo may be more sensitive to regional abnormalities,at least in boys with ADHD,than ALFF.And ALFF may be complementary to ReHo in measuring local spontaneous activity.Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.

Deciphering In-vivo Cross-linking Mass Spectrometry Data for Dynamic Protein Structure Analysis

Protein structure and protein-protein interactions(PPIs)are crucial for regulating cellular activities required for cell viability and homeostasis.Chemical cross-linking coupled with mass spectrometry(CXMS)has become a versatile tool providing insights into both protein structure with distance restraints and protein-protein interactions with interface sites.Cross-links as the most information-rich data in a CXMS experiment are responsible for the structural model validation and integrative modeling with high throughput and sensitivity.In this work,ensemble refinement of the existing protein structure against the in-vivo cross-linking distance restraints was performed for dynamic protein structure modeling and protein interaction binding interface building in the intracellular environment.These results indicate great potential of in-vivo CXMS data for providing a molecular basis of protein structural dynamics exploration and function performance.