• Title/Summary/Keyword: Protein Interaction

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Protein-Protein Interaction Analysis of Corticotropin - Releasing Hormone Receptor 1 with Corticotropin-Releasing Hormone and Sauvagine

  • Nagarajan, Santhosh Kumar
    • Journal of Integrative Natural Science
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    • v.11 no.2
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    • pp.101-106
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    • 2018
  • Corticotropin - releasing hormone receptor 1 (CRHR1) forms an integral part of the pathophysiology of disorders like post-traumatic stress disorder, stress, anxiety, addiction, and depression. Hence it is essential to look for new, potent and structure-specific inhibitors of CRHR1. We have analysed the protein-protein interaction complexes of the CRHR1 receptor with its native ligand CRF and full agonist Sauvagine. The structure of Sauvagine was predicted using homology modelling. We have identified that the residues TYR253, ASP254, GLU256, GLY265, ARG1014 and LY1060 are important in the formation of protein-protein complex formation. Future studies on these residues could throw light on the crucial structural features required for the formation of CRHR1-inhibitor complex and in studies that try to solve the structural complexities of CRHR1.

Advanced techniques of solution nuclear magnetic resonance spectroscopy for structural investigation of protein-protein interaction

  • Sugiki, Toshihiko;Lee, Young-Ho
    • Journal of the Korean Magnetic Resonance Society
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    • v.22 no.4
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    • pp.76-81
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    • 2018
  • Investigation of the protein-protein interaction mode at atomic resolution is essential for understanding on the underlying functional mechanisms of proteins as well as for discovering druggable compounds blocking deleteriou interprotein interactions. Solution NMR spectroscopy provides accurate and precise information on intermolecular interactions even for weak and transient interactions, and it is also markedly useful for examining the change in the conformation and dynamics of target proteins upon binding events. In this mini-review, we comprehensively describe three unique and powerful methods of solution NMR spectroscopy, paramagnetic relaxation enhancement (PRE), pseudo-contact shift (PCS), and residual dipolar coupling (RDC), for the study on protein-protein interactions.

Analysis of a Large-scale Protein Structural Interactome: Ageing Protein structures and the most important protein domain

  • Bolser, Dan;Dafas, Panos;Harrington, Richard;Schroeder, Michael;Park, Jong
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2003.10a
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    • pp.26-51
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    • 2003
  • Large scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in thePDB. PSIMAP incorporates both functional and evolutionary information into a single network. It makes it possible to age protein domains in terms of taxonomic diversity, interaction and function. One consequence of it is to predict the most important protein domain structure in evolution. We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: ${\bullet}$ Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. ${\bullet}$ Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. ${\bullet}$ Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. This led to the prediction of the oldest and most important protein domain in evolution of lift. ${\bullet}$ Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.

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Molecular interaction of $G{\alpha}16$ subunit G protein with chemoattractant receptors

  • Ha, Ji-Hee;Lee, Chang-Ho
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.275.1-275.1
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    • 2002
  • It has been proposed that G protein interacts with receptor via multiple interaction sites. With regard to this, C-terminus of the G${\alpha}$ subunit is clearly not the only structural determinant on the G proteins that is critical for receptor coupling selectivity, but the extreme N-terminus of Ga subunit and other structural elements were proposed to be responsible for dictating the interaction with receptors. (omitted)

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Interaction of Heliothis armigera Nuclear Polyhedrosis Viral Capsid Protein with its Host Actin

  • Lu, Song-Ya;Qi, Yi-Peng;Ge, Guo-Qiong
    • BMB Reports
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    • v.35 no.6
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    • pp.562-567
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    • 2002
  • In order to find the cellular interaction factors of the Heliothis armigera nuclear polyhedrosis virus capsid protein VP39, a Heliothis armigera cell cDNA library was constructed. Then VP39 was used as bait. The host actin gene was isolated from the cDNA library with the yeast two-hybrid system. This demonstrated that VP39 could interact with its host actin in yeast. In order to corroborate this interaction in vivo, the vp39 gene was fused with the green fluorescent protein gene in plasmid pEGFP39. The fusion protein was expressed in the Hz-AM1 cells under the control of the Autographa californica multiple nucleopolyhedrovirus immediate early gene promoter. The host actin was labeled specifically by the red fluorescence substance, tetramethy rhodamine isothicyanete-phalloidin. Observation under a fluorescence microscopy showed that VP39, which was indicated by green fluorescence, began to appear in the cells 6 h after being transfected with pEGFP39. Red actin cables were also formed in the cytoplasm at the same time. Actin was aggregated in the nucleus 9 h after the transfection. The green and red fluorescence always appeared in the same location of the cells, which demonstrated that VP39 could combine with the host actin. Such a combination would result in the actin skeleton rearrangement.

Development of a Novel Cell Surface Attachment System to Display Multi-Protein Complex Using the Cohesin-Dockerin Binding Pair

  • Ko, Hyeok-Jin;Song, Heesang;Choi, In-Geol
    • Journal of Microbiology and Biotechnology
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    • v.31 no.8
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    • pp.1183-1189
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    • 2021
  • Autodisplay of a multimeric protein complex on a cell surface is limited by intrinsic factors such as the types and orientations of anchor modules. Moreover, improper folding of proteins to be displayed often hinders functional cell surface display. While overcoming these drawbacks, we ultimately extended the applicability of the autodisplay platform to the display of a protein complex. We designed and constructed a cell surface attachment (CSA) system that uses a non-covalent protein-protein interaction. We employed the high-affinity interaction mediated by an orthogonal cohesin-dockerin (Coh-Doc) pair from Archaeoglobus fulgidus to build the CSA system. Then, we validated the orthogonal Coh-Doc binding by attaching a monomeric red fluorescent protein to the cell surface. In addition, we evaluated the functional anchoring of proteins fused with the Doc module to the autodisplayed Coh module on the surface of Escherichia coli. The designed CSA system was applied to create a functional attachment of dimeric α-neoagarobiose hydrolase to the surface of E. coli cells.

A Protein-Protein Interaction Extraction Approach Based on Large Pre-trained Language Model and Adversarial Training

  • Tang, Zhan;Guo, Xuchao;Bai, Zhao;Diao, Lei;Lu, Shuhan;Li, Lin
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • v.16 no.3
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    • pp.771-791
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    • 2022
  • Protein-protein interaction (PPI) extraction from original text is important for revealing the molecular mechanism of biological processes. With the rapid growth of biomedical literature, manually extracting PPI has become more time-consuming and laborious. Therefore, the automatic PPI extraction from the raw literature through natural language processing technology has attracted the attention of the majority of researchers. We propose a PPI extraction model based on the large pre-trained language model and adversarial training. It enhances the learning of semantic and syntactic features using BioBERT pre-trained weights, which are built on large-scale domain corpora, and adversarial perturbations are applied to the embedding layer to improve the robustness of the model. Experimental results showed that the proposed model achieved the highest F1 scores (83.93% and 90.31%) on two corpora with large sample sizes, namely, AIMed and BioInfer, respectively, compared with the previous method. It also achieved comparable performance on three corpora with small sample sizes, namely, HPRD50, IEPA, and LLL.

Novel potential drugs for the treatment of primary open-angle glaucoma using protein-protein interaction network analysis

  • Parisima Ghaffarian Zavarzadeh;Zahra Abedi
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.6.1-6.8
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    • 2023
  • Glaucoma is the second leading cause of irreversible blindness, and primary open-angle glaucoma (POAG) is the most common type. Due to inadequate diagnosis, treatment is often not administered until symptoms occur. Hence, approaches enabling earlier prediction or diagnosis of POAG are necessary. We aimed to identify novel drugs for glaucoma through bioinformatics and network analysis. Data from 36 samples, obtained from the trabecular meshwork of healthy individuals and patients with POAG, were acquired from a dataset. Next, differentially expressed genes (DEGs) were identified to construct a protein-protein interaction (PPI) network. In both stages, the genes were enriched by studying the critical biological processes and pathways related to POAG. Finally, a drug-gene network was constructed, and novel drugs for POAG treatment were proposed. Genes with p < 0.01 and |log fold change| > 0.3 (1,350 genes) were considered DEGs and utilized to construct a PPI network. Enrichment analysis yielded several key pathways that were upregulated or downregulated. For example, extracellular matrix organization, the immune system, neutrophil degranulation, and cytokine signaling were upregulated among immune pathways, while signal transduction, the immune system, extracellular matrix organization, and receptor tyrosine kinase signaling were downregulated. Finally, novel drugs including metformin hydrochloride, ixazomib citrate, and cisplatin warrant further analysis of their potential roles in POAG treatment. The candidate drugs identified in this computational analysis require in vitro and in vivo validation to confirm their effectiveness in POAG treatment. This may pave the way for understanding life-threatening disorders such as cancer.

EFFECTS OF DIETARY CELLULOSE AND PROTEIN LEVELS ON NUTRIENT UTILIZATION IN CHICKENS

  • Siri, S.;Tobioka, H.;Tasaki, I.
    • Asian-Australasian Journal of Animal Sciences
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    • v.7 no.2
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    • pp.207-212
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    • 1994
  • Effects of dietary cellulose and protein levels on nutrient utilization in chickens were investigated. Four experimental diets containing 5% (low cellulose) or 20% (high cellulose) cellulose in combination with 10% (low protein) or 20% (high protein) protein of 70 g/day were alternatively forced-fed to eight colostomized White Leghorn cockerels once a day to make $4{\times}4$ Latin-square design. The digestibilities of DM and energy decreased with the increase in cellulose level, but not affected by dietary protein level. Ether extract digestibility was higher in the high cellulose diets than in the low cellulose protein level. Ether extract digestibility was higher in the high cellulose diets than in the low cellulose diets. The digestibility of nitrogen free extract had the same trend with the digestibility of DM and energy. The digestibility of acid detergent fiber was not so much different among the diets, but the NDF digestibility was lower in the high cellulose diets than in the low cellulose diets, due to the low hemicellulose digestibility. The true digestibility of protein was influenced by both of the dietary protein and cellulose levels, and their interaction was found. The dietary protein level affected the biological value of protein but the dietary cellulose level did not, and consequently the biological value of protein in the low protein diets was lower than in the high protein diets.

Protein Kinase A Increases DNA-Binding Activity of Testis-Brain RNA-Binding Protein

  • Ju, Hyun-Hee;Ghil, Sung-Ho
    • Biomedical Science Letters
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    • v.14 no.2
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    • pp.77-81
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    • 2008
  • Testis brain RNA-binding protein (TB-RBP) is a DNA/RNA binding protein. TB-RBP is mainly expressed in testis and brain and highly conserved protein with several functions, including chromosomal translocations, DNA repair, mitotic cell division, and mRNA transport, stabilization, and storage. In our previous study, we identified TB-RBP as an interacting partner for the catalytic subunit $(C{\alpha})$ of protein kinase A(PKA) and verified their interaction with several biochemical analyses. Here, we confirmed interaction between $C{\alpha}$. and TB-RBP in mammalian cells and determined the effect of $C{\alpha}$. on the function of TB-RBP. The activation of $C{\alpha}$. increased the TB-RBP function as a DNA-binding protein. These results suggest that the function of TB-RBP can be modulated by PKA and provide insights into the diverse role of PKA.

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