scholarly journals Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism

2016 ◽  
Vol 44 (1) ◽  
pp. 279-285 ◽  
Author(s):  
M. Merced Malabanan ◽  
Raymond D. Blind
Keyword(s):  
Transcriptional Regulation ◽  
Protein Interactions ◽  
Flexible Substrate ◽  
Short Review ◽  
Inositol Polyphosphate ◽  
Protein Protein Interactions ◽  
Functional Protein ◽  
History Of ◽  
Inositol Polyphosphate Multikinase ◽  
Regulatory Functions

Inositol polyphosphate multikinase (IPMK, ipk2, Arg82, ArgRIII) is an inositide kinase with unusually flexible substrate specificity and the capacity to partake in many functional protein–protein interactions (PPIs). By merging these two activities, IPMK is able to execute gene regulatory functions that are very unique and only now beginning to be recognized. In this short review, we present a brief history of IPMK, describe the structural biology of the enzyme and highlight a few recent discoveries that have shed more light on the role IPMK plays in inositide metabolism, nuclear signalling and transcriptional regulation.

scholarly journals Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer

2021 ◽  
Author(s):  
Erinna F. Lee ◽  
W. Douglas Fairlie
Keyword(s):  
Structural Biology ◽  
Protein Interactions ◽  
Basic Science ◽  
Great Success ◽  
Protein Protein Interactions ◽  
New Class ◽  
Success Stories ◽  
History Of ◽  
Approved Drugs ◽  
Close Relatives

The discovery of a new class of small molecule compounds that target the BCL-2 family of anti-apoptotic proteins is one of the great success stories of basic science leading to translational outcomes in the last 30 years. The eponymous BCL-2 protein was identified over 30 years ago due to its association with cancer. However, it was the unveiling of the biochemistry and structural biology behind it and its close relatives’ mechanism(s)-of-action that provided the inspiration for what are now known as ‘BH3-mimetics’, the first clinically approved drugs designed to specifically inhibit protein–protein interactions. Herein, we chart the history of how these drugs were discovered, their evolution and application in cancer treatment.

scholarly journals Network diffusion on multiple-layers: current approaches and integrative analysis of Rheumatoid Arthritis data.

2017 ◽  
Author(s):  
Noemi Di Nanni ◽  
Matteo Gnocchi ◽  
Marco Moscatelli ◽  
Luciano Milanesi ◽  
Ettore Mosca
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Interactions ◽  
Single Layer ◽  
Joint Analysis ◽  
Protein Protein Interactions ◽  
Functional Protein ◽  
Detection Function ◽  
Module Detection ◽  
Rheumatoid Arthritis Data ◽  
Network Diffusion

Network Diffusion has been proposed in several applications, thanks to its ability of amplifying biological signals and prioritizing genes that may be associated with a disease. Not surprising, the success of Network Diffusion on a “single layer” led to the first approaches for the joint analysis of multi-omics data. Here, we review integrative methods based on Network Diffusion that have been proposed with several aims (e.g. patient stratification, module detection, function prediction). We used Network Diffusion to analyse, in the context of physical and functional protein-protein interactions, genetic variation, DNA methylation and gene expression data from a study on Rheumatoid Arthritis. We identified functionally related genes with multiple alterations.

scholarly journals TRI_tool: a web-tool for prediction of protein–protein interactions in human transcriptional regulation

2016 ◽  
Vol 33 (2) ◽  
pp. 289-291 ◽  
Author(s):  
Vladimir Perovic ◽  
Neven Sumonja ◽  
Branislava Gemovic ◽  
Eneda Toska ◽  
Stefan G. Roberts ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Web Tool

scholarly journals Molecular Dynamics-Guided Design of a Functional Protein–ATRP Conjugate That Eliminates Protein–Protein Interactions

2021 ◽  
Vol 32 (4) ◽  
pp. 821-832
Author(s):  
Bibifatima Kaupbayeva ◽  
Susanne Boye ◽  
Aravinda Munasinghe ◽  
Hironobu Murata ◽  
Krzysztof Matyjaszewski ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Functional Protein

scholarly journals PPI-MASS: An Interactive Web Server to Identify Protein-Protein Interactions From Mass Spectrometry-Based Proteomics Data

2021 ◽  
Vol 8 ◽  
Author(s):  
Mariela González-Avendaño ◽  
Simón Zúñiga-Almonacid ◽  
Ian Silva ◽  
Boris Lavanderos ◽  
Felipe Robinson ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Web Server ◽  
Target Protein ◽  
Protein Protein Interactions ◽  
Proteomics Data ◽  
Functional Protein ◽  
Web Platform ◽  
The Web

Mass spectrometry-based proteomics methods are widely used to identify and quantify protein complexes involved in diverse biological processes. Specifically, tandem mass spectrometry methods represent an accurate and sensitive strategy for identifying protein-protein interactions. However, most of these approaches provide only lists of peptide fragments associated with a target protein, without performing further analyses to discriminate physical or functional protein-protein interactions. Here, we present the PPI-MASS web server, which provides an interactive analytics platform to identify protein-protein interactions with pharmacological potential by filtering a large protein set according to different biological features. Starting from a list of proteins detected by MS-based methods, PPI-MASS integrates an automatized pipeline to obtain information of each protein from freely accessible databases. The collected data include protein sequence, functional and structural properties, associated pathologies and drugs, as well as location and expression in human tissues. Based on this information, users can manipulate different filters in the web platform to identify candidate proteins to establish physical contacts with a target protein. Thus, our server offers a simple but powerful tool to detect novel protein-protein interactions, avoiding tedious and time-consuming data postprocessing. To test the web server, we employed the interactome of the TRPM4 and TMPRSS11a proteins as a use case. From these data, protein-protein interactions were identified, which have been validated through biochemical and bioinformatic studies. Accordingly, our web platform provides a comprehensive and complementary tool for identifying protein-protein complexes assisting the future design of associated therapies.

scholarly journals The structural evolution of host-pathogen protein interactions: an integrative approach

2019 ◽  
Author(s):  
Anderson F. Brito ◽  
John W. Pinney
Keyword(s):  
Protein Interactions ◽  
Homology Modelling ◽  
Structural Evolution ◽  
Integrative Approach ◽  
Binding Affinities ◽  
Protein Protein Interactions ◽  
Host Pathogen ◽  
Cell Membrane Proteins ◽  
Pathogen Protein ◽  
History Of

ABSTRACTThe evolution of protein-protein interactions (PPIs) is directly influenced by the evolutionary histories of the genes and the species encoding the interacting proteins. When it comes to PPIs of host-pathogen systems, the complexity of their evolution is much higher, as two independent, but biologically associated entities, are involved. In this work, an integrative approach combining phylogenetics, tree reconciliations, ancestral sequence reconstructions, and homology modelling is proposed for studying the evolution of host-pathogen PPIs. As a case study, we analysed the evolution of interactions between herpesviral glycoproteins gD/gG and the cell membrane proteins nectins. By modelling the structures of more than 12,000 ancestral states of these virus-host complexes it was found that in early times of their evolution, these proteins were unable to interact, most probably due to electrostatic incompatibilities between their interfaces. After the event of gene duplication that gave rise to a paralog of gD (known as gG), both protein lineages evolved following distinct functional constraints, with most gD reaching high binding affinities towards nectins, while gG lost such ability, most probably due to a process of neofunctionalization. Based on their favourable interaction energies (negative ΔG), it is possible to hypothesize that apart from nectins 1 and 2, some alphaherpesviruses might also use nectins 3 and 4 as cell receptors. These findings show that the proposed integrative method is suitable for modelling the evolution of host-pathogen protein interactions, and useful for raising new hypotheses that broaden our understanding about the evolutionary history of PPIs, and their molecular functioning.

scholarly journals Lipid signaling to membrane proteins: From second messengers to membrane domains and adapter-free endocytosis

2018 ◽  
Vol 150 (2) ◽  
pp. 211-224 ◽  
Author(s):  
Donald W. Hilgemann ◽  
Gucan Dai ◽  
Anthony Collins ◽  
Vincenzo Larricia ◽  
Simona Magi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Second Messengers ◽  
Surface Membrane ◽  
Short Review ◽  
Lipid Signaling ◽  
Membrane Domains ◽  
Protein Protein Interactions ◽  
Protein Membrane ◽  
Bona Fide ◽  
And Control

Lipids influence powerfully the function of ion channels and transporters in two well-documented ways. A few lipids act as bona fide second messengers by binding to specific sites that control channel and transporter gating. Other lipids act nonspecifically by modifying the physical environment of channels and transporters, in particular the protein–membrane interface. In this short review, we first consider lipid signaling from this traditional viewpoint, highlighting innumerable Journal of General Physiology publications that have contributed to our present understanding. We then switch to our own emerging view that much important lipid signaling occurs via the formation of membrane domains that influence the function of channels and transporters within them, promote selected protein–protein interactions, and control the turnover of surface membrane.

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