scholarly journals Synthesis of fluorinated maltose derivatives for monitoring protein interaction by 19F NMR

2012 ◽  
Vol 8 ◽  
pp. 448-455 ◽  
Author(s):  
Michaela Braitsch ◽  
Hanspeter Kählig ◽  
Georg Kontaxis ◽  
Michael Fischer ◽  
Toshinari Kawada ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Binding Protein ◽  
Maltose Binding Protein ◽  
Interaction Patterns ◽  
Protein Protein Interactions ◽  
Reporter System ◽  
Perfect Agreement ◽  
Ligand Interaction ◽  
Chemical Shift Data

A novel reporter system, which is applicable to the 19F NMR investigation of protein interactions, is presented. This approach uses 2-F-labeled maltose as a spy ligand to indirectly probe protein–ligand or protein–protein interactions of proteins fused or tagged to the maltose-binding protein (MBP). The key feature is the simultaneous NMR observation of both 19F NMR signals of gluco/manno-type-2-F-maltose-isomers; one isomer (α-gluco-type) binds to MBP and senses the protein interaction, and the nonbinding isomers (β-gluco- and/or α/β-manno-type) are utilized as internal references. Moreover, this reporter system was used for relative affinity studies of fluorinated and nonfluorinated carbohydrates to the maltose-binding protein, which were found to be in perfect agreement with published X-ray data. The results of the NMR competition experiments together with the established correlation between 19F chemical shift data and molecular interaction patterns, suggest valuable applications for studies of protein–ligand interaction interfaces.

scholarly journals A multitask transfer learning framework for the prediction of virus-human protein–protein interactions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Thi Ngan Dong ◽  
Graham Brogden ◽  
Gisa Gerold ◽  
Megha Khosla
Keyword(s):  
Transfer Learning ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Sequences ◽  
Human Protein ◽  
Interaction Patterns ◽  
Protein Protein Interactions ◽  
Interaction Prediction ◽  
Protein Protein Interaction ◽  
Protein Interaction Prediction

Abstract Background Viral infections are causing significant morbidity and mortality worldwide. Understanding the interaction patterns between a particular virus and human proteins plays a crucial role in unveiling the underlying mechanism of viral infection and pathogenesis. This could further help in prevention and treatment of virus-related diseases. However, the task of predicting protein–protein interactions between a new virus and human cells is extremely challenging due to scarce data on virus-human interactions and fast mutation rates of most viruses. Results We developed a multitask transfer learning approach that exploits the information of around 24 million protein sequences and the interaction patterns from the human interactome to counter the problem of small training datasets. Instead of using hand-crafted protein features, we utilize statistically rich protein representations learned by a deep language modeling approach from a massive source of protein sequences. Additionally, we employ an additional objective which aims to maximize the probability of observing human protein–protein interactions. This additional task objective acts as a regularizer and also allows to incorporate domain knowledge to inform the virus-human protein–protein interaction prediction model. Conclusions Our approach achieved competitive results on 13 benchmark datasets and the case study for the SARS-CoV-2 virus receptor. Experimental results show that our proposed model works effectively for both virus-human and bacteria-human protein–protein interaction prediction tasks. We share our code for reproducibility and future research at https://git.l3s.uni-hannover.de/dong/multitask-transfer.

An efficient transient assays system using Agrobacterium-mediated transformation of onion (Allium cepa) epidermal cells

2020 ◽  
Vol 80 (03) ◽  
Author(s):  
Yu-Miao Zhang ◽  
Jun Wang ◽  
Tao Wu
Keyword(s):  
Subcellular Localization ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Epidermal Cells ◽  
Cyclin Dependent Kinase ◽  
Protein Subcellular Localization ◽  
Protein Protein Interactions ◽  
Efficient System ◽  
Protein Protein Interaction ◽  
Onion Epidermal Cells

In this study, the Agrobacterium infection medium, infection duration, detergent, and cell density were optimized. The sorghum-based infection medium (SbIM), 10-20 min infection time, addition of 0.01% Silwet L-77, and Agrobacterium optical density at 600 nm (OD600), improved the competence of onion epidermal cells to support Agrobacterium infection at >90% efficiency. Cyclin-dependent kinase D-2 (CDKD-2) and cytochrome c-type biogenesis protein (CYCH), protein-protein interactions were localized. The optimized procedure is a quick and efficient system for examining protein subcellular localization and protein-protein interaction.

Protein Interaction Domains and Post-Translational Modifications: Structural Features and Drug Discovery Applications

2020 ◽  
Vol 27 (37) ◽  
pp. 6306-6355 ◽  
Author(s):  
Marian Vincenzi ◽  
Flavia Anna Mercurio ◽  
Marilisa Leone
Keyword(s):  
Drug Discovery ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Protein Complexes ◽  
Structural Features ◽  
Protein Protein Interactions ◽  
Modular Architecture ◽  
Post Translational Modifications ◽  
Interaction Domains

Background:: Many pathways regarding healthy cells and/or linked to diseases onset and progression depend on large assemblies including multi-protein complexes. Protein-protein interactions may occur through a vast array of modules known as protein interaction domains (PIDs). Objective:: This review concerns with PIDs recognizing post-translationally modified peptide sequences and intends to provide the scientific community with state of art knowledge on their 3D structures, binding topologies and potential applications in the drug discovery field. Method:: Several databases, such as the Pfam (Protein family), the SMART (Simple Modular Architecture Research Tool) and the PDB (Protein Data Bank), were searched to look for different domain families and gain structural information on protein complexes in which particular PIDs are involved. Recent literature on PIDs and related drug discovery campaigns was retrieved through Pubmed and analyzed. Results and Conclusion:: PIDs are rather versatile as concerning their binding preferences. Many of them recognize specifically only determined amino acid stretches with post-translational modifications, a few others are able to interact with several post-translationally modified sequences or with unmodified ones. Many PIDs can be linked to different diseases including cancer. The tremendous amount of available structural data led to the structure-based design of several molecules targeting protein-protein interactions mediated by PIDs, including peptides, peptidomimetics and small compounds. More studies are needed to fully role out, among different families, PIDs that can be considered reliable therapeutic targets, however, attacking PIDs rather than catalytic domains of a particular protein may represent a route to obtain selective inhibitors.

c-Fos-induced activation of a TATA-box-containing promoter involves direct contact with TATA-box-binding protein

1994 ◽  
Vol 14 (9) ◽  
pp. 6021-6029
Author(s):  
R Metz ◽  
A J Bannister ◽  
J A Sutherland ◽  
C Hagemeier ◽  
E C O'Rourke ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Transcriptional Activation ◽  
Binding Protein ◽  
Tata Box ◽  
Binding Motif ◽  
Protein Protein Interactions ◽  
High Concentrations ◽  
Tata Box Binding Protein

Transcriptional activation in eukaryotes involves protein-protein interactions between regulatory transcription factors and components of the basal transcription machinery. Here we show that c-Fos, but not a related protein, Fra-1, can bind the TATA-box-binding protein (TBP) both in vitro and in vivo and that c-Fos can also interact with the transcription factor IID complex. High-affinity binding to TBP requires c-Fos activation modules which cooperate to activate transcription. One of these activation modules contains a TBP-binding motif (TBM) which was identified through its homology to TBP-binding viral activators. This motif is required for transcriptional activation, as well as TBP binding. Domain swap experiments indicate that a domain containing the TBM can confer TBP binding on Fra-1 both in vitro and in vivo. In vivo activation experiments indicate that a GAL4-Fos fusion can activate a promoter bearing a GAL4 site linked to a TATA box but that this activity does not occur at high concentrations of GAL4-Fos. This inhibition (squelching) of c-Fos activity is relieved by the presence of excess TBP, indicating that TBP is a direct functional target of c-Fos. Removing the TBM from c-Fos severely abrogates activation of a promoter containing a TATA box but does not affect activation of a promoter driven only by an initiator element. Collectively, these results suggest that c-Fos is able to activate via two distinct mechanisms, only one of which requires contact with TBP. Since TBP binding is not exhibited by Fra-1, TBP-mediated activation may be one characteristic that discriminates the function of Fos-related proteins.

A crosslinked and ribosylated actin trimer does not interact productively with myosin

2019 ◽  
Vol 97 (2) ◽  
pp. 140-147 ◽  
Author(s):  
Navneet Sidhu ◽  
John F. Dawson
Keyword(s):  
Binding Site ◽  
Protein Interactions ◽  
Binding Proteins ◽  
Binding Protein ◽  
Dnase I ◽  
Protein Protein Interactions ◽  
Adp Ribosylation ◽  
Myosin Binding ◽  
Pointed End

A purified F-actin-derived actin trimer that interacts with end-binding proteins did not activate or bind the side-binding protein myosin under rigor conditions. Remodeling of the actin trimer by the binding of gelsolin did not rescue myosin binding, nor did the use of different means of inhibiting the polymerization of the trimer. Our results demonstrate that ADP-ribosylation on all actin subunits of an F-actin-derived trimer inhibits myosin binding and that the binding of DNase-I to the pointed end subunits of a crosslinked trimer also remodels the myosin binding site. Taken together, this work highlights the need for a careful balance between modification of actin subunits and maintaining protein–protein interactions to produce a physiologically relevant short F-actin complex.

Furan warheads for covalent trapping of weak protein-protein interactions: cross-linking of thymosin β4 to actin

2021 ◽  
Author(s):  
Laia Miret Casals ◽  
Willem Vannecke ◽  
Kurt Hoogewijs ◽  
Gianluca Arauz ◽  
Marina Gay ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
3D Structure ◽  
Cross Linking ◽  
Thymosin Β4 ◽  
Protein Protein Interactions ◽  
Site Specific ◽  
Protein Protein Interaction ◽  
Covalent Trapping

We describe furan as a triggerable ‘warhead’ for site-specific cross-linking using the actin and thymosin β4 (Tβ4)-complex as model of a weak and dynamic protein-protein interaction with known 3D structure...

scholarly journals Virion-Wide Protein Interactions of Kaposi's Sarcoma-Associated Herpesvirus

2008 ◽  
Vol 82 (10) ◽  
pp. 4742-4750 ◽  
Author(s):  
Ramona Rozen ◽  
Narayanan Sathish ◽  
Yong Li ◽  
Yan Yuan
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Capsid Proteins ◽  
Protein Protein Interactions ◽  
Virion Assembly ◽  
Tegument Proteins ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT Herpesvirus virions are highly organized structures built through specific protein-protein interactions. Thus, revelation of the protein interactions among virion proteins will shed light on the processes and the mechanisms of virion formation. Recently, we identified 24 virion proteins of Kaposi's sarcoma-associated herpesvirus (KSHV), using a proteomic approach (F. X. Zhu et al., J. Virol. 79:800-811, 2005). In the current study, a comprehensive analysis of protein-protein interaction between KSHV virion proteins was carried out using yeast two-hybrid (Y2H) and coimmunoprecipitation (co-IP) approaches. Every pairwise combination between KSHV tegument and capsid proteins, between tegument and envelope proteins, and among tegument proteins was tested for possible binary interaction. Thirty-seven protein-protein interactions were identified by both Y2H and co-IP analyses. The results revealed interactions between tegument and capsid proteins such as that of open reading frame 64 (ORF64) with ORF25 (major capsid protein [MCP]), ORF62 (triplex-1 [TRI-1]), and ORF26 (TRI-2). Many interactions were detected among the tegument proteins. ORF64 was found to interact with several tegument proteins including ORF11, ORF21, ORF33, ORF45, ORF63, ORF75, and ORF64 itself, suggesting that ORF64 may serve as a hub protein and play a role in recruiting tegument proteins during tegumentation and virion assembly. Our investigation also revealed redundant interactions between tegument proteins and envelope glycoproteins. These interactions are believed to contribute to final envelopment in virion assembly. Overall, this study allows us to establish a virion-wide protein interaction map, which provides insight into the architecture of the KSHV virion and sets up a foundation for exploring the functions of these proteins in viral particle assembly.

scholarly journals HMNPPID—human malignant neoplasm protein–protein interaction database

2019 ◽  
Vol 13 (S1) ◽  
Author(s):  
Qingqing Li ◽  
Zhihao Yang ◽  
Zhehuan Zhao ◽  
Ling Luo ◽  
Zhiheng Li ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Malignant Neoplasm ◽  
Biomedical Literature ◽  
Malignant Neoplasms ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Interaction Database ◽  
Protein Interaction Database

Abstract Background Protein–protein interaction (PPI) information extraction from biomedical literature helps unveil the molecular mechanisms of biological processes. Especially, the PPIs associated with human malignant neoplasms can unveil the biology behind these neoplasms. However, such PPI database is not currently available. Results In this work, a database of protein–protein interactions associated with 171 kinds of human malignant neoplasms named HMNPPID is constructed. In addition, a visualization program, named VisualPPI, is provided to facilitate the analysis of the PPI network for a specific neoplasm. Conclusions HMNPPID can hopefully become an important resource for the research on PPIs of human malignant neoplasms since it provides readily available data for healthcare professionals. Thus, they do not need to dig into a large amount of biomedical literatures any more, which may accelerate the researches on the PPIs of malignant neoplasms.

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