scholarly journals Hidden information on protein function in censuses of proteome foldedness

2021 ◽  
Author(s):  
Dezerae Cox ◽  
Ching-Seng Ang ◽  
Nadinath B. Nillegoda ◽  
Gavin E. Reid ◽  
Danny M. Hatters
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Ligand Binding ◽  
Protein Function ◽  
Hidden Information ◽  
Unfolded Protein ◽  
Cofactor Binding ◽  
Cell Lysate ◽  
Protein Chaperone ◽  
Biological Milieu

AbstractMethods that assay protein foldedness with proteomics have generated censuses of protein folding stabilities in biological milieu. Surprisingly, different censuses poorly correlate with each other. Here, we show that methods targeting foldedness through monitoring amino acid sidechain reactivity also detect changes in conformation and ligand binding. About one quarter of cysteine or methionine sidechains in proteins in mammalian cell lysate increase in reactivity upon chemical denaturant titration consistent with two-state unfolding. Paradoxically, up to one third decreased reactivity, which were enriched in proteins with functions relating to unfolded protein stress. One protein, chaperone HSPA8, displayed changes arising from ligand and cofactor binding. Unmasking this hidden information should improve efforts to understand both folding and the remodeling of protein function directly in complex biological settings.One Sentence SummaryWe show that proteome folding stability censuses are ill-defined because they earmark hidden information on conformation and ligand binding.

Spatial localization of unknown proteins in the endoplasmic reticulum predicts functions

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Michael D. Jain ◽  
Hisao Nagaya ◽  
Annalyn Gilchrist ◽  
Miroslaw Cygler ◽  
John J.M. Bergeron
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Protein Function ◽  
Protein Translocation ◽  
Spatial Localization ◽  
Predict Protein Function ◽  
Insight Into ◽  
Soluble Fractions ◽  
Er Membrane

Protein synthesis, folding and degradation functions are spatially segregated in the endoplasmic reticulum (ER) with respect to the membrane and the ribosome (rough and smooth ER). Interrogation of a proteomics resource characterizing rough and smooth ER membranes subfractionated into cytosolic, membrane, and soluble fractions gives a spatial map of known proteins involved in ER function. The spatial localization of 224 identified unknown proteins in the ER is predicted to give insight into their function. Here we provide evidence that the proteomics resource accurately predicts the function of new proteins involved in protein synthesis (nudilin), protein translocation across the ER membrane (nicalin), co-translational protein folding (stexin), and distal protein folding in the lumen of the ER (erlin-1, TMX2). Proteomics provides the spatial localization of proteins and can be used to accurately predict protein function.

Predicting Protein Folding Rate From Amino Acid Sequence

2011 ◽  
Vol 37 (12) ◽  
pp. 1331-1338 ◽  
Author(s):  
Jian-Xiu GUO ◽  
Ni-Ni RAO ◽  
Guang-Xiong LIU ◽  
Jie LI ◽  
Yun-He WANG
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Folding Rate ◽  
Protein Folding Rate

Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Amir Taherkhani ◽  
Athena Orangi ◽  
Shirin Moradkhani ◽  
Zahra Khamverdi
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Amino Acid ◽  
Matrix Metalloproteinase ◽  
Ligand Binding ◽  
Chronic Inflammation ◽  
Cancer Progression ◽  
Dimensional Structure ◽  
Control Test ◽  
Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

Protein Folding Kinetic Order Prediction from Amino Acid Sequence Based on Horizontal Visibility Network

2016 ◽  
Vol 11 (2) ◽  
pp. 173-185 ◽  
Author(s):  
Zhi-Qin Zhao ◽  
Zu-Guo Yu ◽  
Vo Anh ◽  
Jing-Yang Wu ◽  
Guo-Sheng Han
Keyword(s):  
Protein Folding ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Horizontal Visibility ◽  
Kinetic Order

scholarly journals Avoided motifs: short amino acid strings missing from protein datasets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Function ◽  
Large Protein ◽  
New Approach ◽  
Cellular Context ◽  
Human Proteins ◽  
Context Specific ◽  
Protein Datasets

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.

scholarly journals The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erna Davydova ◽  
Tadahiro Shimazu ◽  
Maren Kirstin Schuhmacher ◽  
Magnus E. Jakobsson ◽  
Hanneke L. D. M. Willemen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Protein Function ◽  
Crucial Role ◽  
Complex I ◽  
Protein Modification ◽  
Zinc Binding ◽  
Functional Studies ◽  
Mitochondrial Respiratory Complex ◽  
Respiratory Complex I ◽  
Broad Specificity

AbstractPost-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where “x” is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.

scholarly journals Phylogenetic analysis and predicted functional effect of protein mutations of E6 and E7 HPV16 strains isolated in Indonesia

2015 ◽  
Vol 24 (4) ◽  
pp. 197-205
Author(s):  
Dwi Wulandari ◽  
Lisnawati Rachmadi ◽  
Tjahjani M. Sudiro
Keyword(s):  
Amino Acids ◽  
Phylogenetic Analysis ◽  
Amino Acid ◽  
Asian American ◽  
Protein Function ◽  
Single Amino Acid ◽  
Hpv16 E6 ◽  
E6 And E7 ◽  
Neutral Mutations

Background: E6 and E7 are oncoproteins of HPV16. Natural amino acid variation in HPV16 E6 can alter its carcinogenic potential. The aim of this study was to analyze phylogenetically E6 and E7 genes and proteins of HPV16 from Indonesia and predict the effects of single amino acid substitution on protein function. This analysis could be used to reduce time, effort, and research cost as initial screening in selection of protein or isolates to be tested in vitro or in vivo.Methods: In this study, E6 and E7 gene sequences were obtained from 12 samples of  Indonesian isolates, which  were compared with HPV16R (prototype) and 6 standard isolates in the category of European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and North American (NA) branch from Genbank. Bioedit v.7.0.0 was used to analyze the composition and substitution of single amino acids. Phylogenetic analysis of E6 and E7 genes and proteins was performed using Clustal X (1.81) and NJPLOT softwares. Effects of single amino acid substitutions on protein function of E6 and E7 were analysed by SNAP.Results: Java variants and isolate ui66* belonged to European branch, while the others belonged to Asian and African branches. Twelve changes of amino acids were found in E6 and one in E7 proteins. SNAP analysis showed two non neutral mutations, i.e. R10I and C63G in E6 proteins. R10I mutations were found in Af-2 genotype (AF472509) and Indonesian isolates (Af2*), while C63G mutation was found only in Af2*.Conclusion: E6 proteins of HPV16 variants were more variable than E7. SNAP analysis showed that only E6 protein of African-2 branch had functional differences compared to HPV16R.

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