scholarly journals The Role of Meningococcal Porin B in Protein-Protein Interactions with Host Cells

2018 ◽  
Vol 62 (1) ◽  
pp. 52-58
Author(s):  
E. Káňová ◽  
I. Jiménez-Munguía ◽  
Ľ. Čomor ◽  
Z. Tkáčová ◽  
I. Širochmanová ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Cell Signalling ◽  
Structure And Function ◽  
Host Cells ◽  
Protein Protein Interactions ◽  
Receptor Interactions ◽  
And Function ◽  
Fatal Sepsis ◽  
Porin B

Abstract Neisseria meningitidis is a Gram-negative diplococcus responsible for bacterial meningitis and fatal sepsis. Ligand-receptor interactions are one of the main steps in the development of neuroinvasion. Porin B (PorB), neisserial outer membrane protein (ligand), binds to host receptors and triggers many cell signalling cascades allowing the meningococcus to damage the host cells or induce immune cells responses via the TLR2-dependent mechanisms. In this paper, we present a brief review of the structure and function of PorB.

scholarly journals A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function.

1995 ◽  
Vol 15 (10) ◽  
pp. 5214-5225 ◽  
Author(s):  
A D Catling ◽  
H J Schaeffer ◽  
C W Reuter ◽  
G R Reddy ◽  
M J Weber
Keyword(s):  
Protein Interactions ◽  
Critical Role ◽  
Phosphorylation Site ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Serum Stimulation ◽  
And Function

Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and SEKs activated independently of Raf, we sought to investigate the role of this sequence in MEK1 and MEK2 regulation and function. Deletion of the PR sequence from MEK1 blocked the ability of MEK1 to associate with members of the Raf family and markedly attenuated activation of the protein in vivo following growth factor stimulation. In addition, this sequence was necessary for efficient activation of MEK1 in vitro by B-Raf but dispensable for activation by a novel MEK1 activator which we have previously detected in fractionated fibroblast extracts. Furthermore, we found that a phosphorylation site within the PR sequence of MEK1 was required for sustained MEK1 activity in response to serum stimulation of quiescent fibroblasts. Consistent with this observation, we observed that MEK2, which lacks a phosphorylation site at the corresponding position, was activated only transiently following serum stimulation. Finally, we found that deletion of the PR sequence from a constitutively activated MEK1 mutant rendered the protein nontransforming in Rat1 fibroblasts. These observations indicate a critical role for the PR sequence in directing specific protein-protein interactions important for the activation, inactivation, and downstream functioning of the MEKs.

scholarly journals Emerging Concepts and Functions of Autophagy as a Regulator of Synaptic Components and Plasticity

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 34 ◽  
Author(s):  
YongTian Liang
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Protein Protein Interactions ◽  
Neuronal Function ◽  
And Function ◽  
Cellular Components ◽  
Neuronal Autophagy

Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity.

Recent trends in QSAR in Modelling of Drug-Protein and Protein-Protein Interactions

2020 ◽  
Vol 23 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Chemical Space ◽  
3D Qsar ◽  
Protein Protein Interactions ◽  
Lead Compounds ◽  
Receptor Interactions ◽  
Recent Trends ◽  
Drug Receptor

: The unprecedented growth in the area of QSAR has completely changed the landscape of drug discovery. QSAR techniques quantitatively correlate the associations between chemical structure alterations and respective changes in biological activity, thereby playing a major role in improving the potency, efficacy and selectivity of the lead compounds in drug design. In this review, authors have summarized the role of QSAR in drug discovery, especially with respect to lead optimization and drug-receptor interactions. The recent trends in the usage of 3D-QSAR to understand protein-Protein Interactions (PPIs) have been explored. Specifically, the latest advances in the concepts of chemical Space (CS) and chemography have been examined in detail. Also, the authors have tried to present the current limitations and challenges in this field. The authors agree with the prevalent view that the models must be systematically validated both internally as well as externally to strengthen the hit rates in the experiments. It is important to apply the ‘in cerebro-in silico’ approach that entails choosing the method specific to the target–ligand system.

scholarly journals The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin

2021 ◽  
Vol 22 (4) ◽  
pp. 1727
Author(s):  
Kristina Kastano ◽  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Low Complexity ◽  
Protein Interaction Data ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Evolutionarily Conserved ◽  
And Function

Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a growing number of reports on their function in protein interactions regulated by post-translational modifications. LCRs facilitate the increase of regulatory and network complexity required with the emergence of organisms with more complex tissue distribution and development. Although the low conservation and structural flexibility of LCRs complicate their study, evolutionary studies of proteins across species have been used to evaluate their significance and function. To investigate how to apply this evolutionary approach to the study of LCR function in protein–protein interactions, we performed a detailed analysis for Huntingtin (HTT), a large protein that is a hub for interaction with hundreds of proteins, has a variety of LCRs, and for which partial structural information (in complex with HAP40) is available. We hypothesize that proteins RASA1, SYN2, and KAT2B may compete with HAP40 for their attachment to the core of HTT using similar LCRs. Our results illustrate how evolution might favor the interplay of LCRs with domains, and the possibility of detecting multiple modes of LCR-mediated protein–protein interactions with a large hub such as HTT when enough protein interaction data is available.

scholarly journals Survey of Natural Language Processing Techniques in Bioinformatics

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Zhiqiang Zeng ◽  
Hua Shi ◽  
Yun Wu ◽  
Zhiling Hong
Keyword(s):  
Natural Language Processing ◽  
Text Mining ◽  
Natural Language ◽  
Language Processing ◽  
Protein Interactions ◽  
Noncoding Rna ◽  
Structure And Function ◽  
Protein Protein Interactions ◽  
And Function ◽  
Processing Techniques

Informatics methods, such as text mining and natural language processing, are always involved in bioinformatics research. In this study, we discuss text mining and natural language processing methods in bioinformatics from two perspectives. First, we aim to search for knowledge on biology, retrieve references using text mining methods, and reconstruct databases. For example, protein-protein interactions and gene-disease relationship can be mined from PubMed. Then, we analyze the applications of text mining and natural language processing techniques in bioinformatics, including predicting protein structure and function, detecting noncoding RNA. Finally, numerous methods and applications, as well as their contributions to bioinformatics, are discussed for future use by text mining and natural language processing researchers.

scholarly journals The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Wallace H Liu ◽  
Sarah C Roemer ◽  
Yeyun Zhou ◽  
Zih-Jie Shen ◽  
Briana K Dennehey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Histone Chaperone ◽  
Protein Protein Interactions ◽  
Rich Domain ◽  
C Terminus ◽  
Assembly Factor ◽  
Hydrogen Deuterium ◽  
And Function ◽  
Minimal Region

The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone not only binds H3/H4 with high affinity, but also promotes histone tetramerization independent of the other subunits. Moreover, we identify a minimal region in the C-terminus of Cac1, including the structured winged helix domain and glutamate/aspartate-rich domain, which is sufficient to induce (H3/H4)2 tetramerization. These findings reveal a key role of Cac1 in histone tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic replication.

scholarly journals Heparan Sulfate Biosynthesis and Sulfation Profiles as Modulators of Cancer Signalling and Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Catarina Marques ◽  
Celso A. Reis ◽  
Romain R. Vivès ◽  
Ana Magalhães
Keyword(s):  
Heparan Sulfate ◽  
Protein Interactions ◽  
Cell Signalling ◽  
Structural Diversity ◽  
Structural Features ◽  
Protein Protein Interactions ◽  
Cellular Events ◽  
And Function ◽  
The Impact ◽  
Cell Cell

Heparan Sulfate Proteoglycans (HSPGs) are important cell surface and Extracellular Matrix (ECM) maestros involved in the orchestration of multiple cellular events in physiology and pathology. These glycoconjugates bind to various bioactive proteins via their Heparan Sulfate (HS) chains, but also through the protein backbone, and function as scaffolds for protein-protein interactions, modulating extracellular ligand gradients, cell signalling networks and cell-cell/cell-ECM interactions. The structural features of HS chains, including length and sulfation patterns, are crucial for the biological roles displayed by HSPGs, as these features determine HS chains binding affinities and selectivity. The large HS structural diversity results from a tightly controlled biosynthetic pathway that is differently regulated in different organs, stages of development and pathologies, including cancer. This review addresses the regulatory mechanisms underlying HS biosynthesis, with a particular focus on the catalytic activity of the enzymes responsible for HS glycan sequences and sulfation motifs, namely D-Glucuronyl C5-Epimerase, N- and O-Sulfotransferases. Moreover, we provide insights on the impact of different HS structural epitopes over HSPG-protein interactions and cell signalling, as well as on the effects of deregulated expression of HS modifying enzymes in the development and progression of cancer. Finally, we discuss the clinical potential of HS biosynthetic enzymes as novel targets for therapy, and highlight the importance of developing new HS-based tools for better patients’ stratification and cancer treatment.

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