Protein Interactions for Functional Genomics

2012 ◽  
Vol 3 (4) ◽  
pp. 15-30
Author(s):  
Pablo Minguez ◽  
Joaquin Dopazo
Keyword(s):  
Graph Theory ◽  
Protein Interactions ◽  
Biological Networks ◽  
State Of The Art ◽  
Protein Protein Interactions ◽  
Pairwise Interactions ◽  
Novel Approach ◽  
Functional Profiling ◽  
Available Resources

Here the authors review the state of the art in the use of protein-protein interactions (ppis) within the context of the interpretation of genomic experiments. They report the available resources and methodologies used to create a curated compilation of ppis introducing a novel approach to filter interactions. Special attention is paid in the complexity of the topology of the networks formed by proteins (nodes) and pairwise interactions (edges). These networks can be studied using graph theory and a brief introduction to the characterization of biological networks and definitions of the more used network parameters is also given. Also a report on the available resources to perform different modes of functional profiling using ppi data is provided along with a discussion on the approaches that have typically been applied into this context. They also introduce a novel methodology for the evaluation of networks and some examples of its application.

Protein Interactions for Functional Genomics

2009 ◽  
pp. 223-238 ◽  
Author(s):  
Pablo Minguez ◽  
Joaquin Dopazo
Keyword(s):  
Graph Theory ◽  
Functional Genomics ◽  
Protein Interactions ◽  
Biological Networks ◽  
Protein Protein Interactions ◽  
Pairwise Interactions ◽  
Novel Approach ◽  
Functional Profiling ◽  
Available Resources

Here the authors review the state of the art in the use of protein-protein interactions (ppis) within the context of the interpretation of genomic experiments. They report the available resources and methodologies used to create a curated compilation of ppis introducing a novel approach to filter interactions. Special attention is paid in the complexity of the topology of the networks formed by proteins (nodes) and pairwise interactions (edges). These networks can be studied using graph theory and a brief introduction to the characterization of biological networks and definitions of the more used network parameters is also given. Also a report on the available resources to perform different modes of functional profiling using ppi data is provided along with a discussion on the approaches that have typically been applied into this context. They also introduce a novel methodology for the evaluation of networks and some examples of its application.

Algorithmic and Stochastic Representations of Gene Regulatory Networks and Protein-Protein Interactions

2019 ◽  
Vol 19 (6) ◽  
pp. 413-425 ◽  
Author(s):  
Athanasios Alexiou ◽  
Stylianos Chatzichronis ◽  
Asma Perveen ◽  
Abdul Hafeez ◽  
Ghulam Md. Ashraf
Keyword(s):  
Protein Interactions ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Review Paper ◽  
Boolean Networks ◽  
Diagnostic Tools ◽  
Complex Nature ◽  
Cellular Interactions ◽  
Protein Protein Interactions ◽  
Deterministic Models

Background:Latest studies reveal the importance of Protein-Protein interactions on physiologic functions and biological structures. Several stochastic and algorithmic methods have been published until now, for the modeling of the complex nature of the biological systems.Objective:Biological Networks computational modeling is still a challenging task. The formulation of the complex cellular interactions is a research field of great interest. In this review paper, several computational methods for the modeling of GRN and PPI are presented analytically.Methods:Several well-known GRN and PPI models are presented and discussed in this review study such as: Graphs representation, Boolean Networks, Generalized Logical Networks, Bayesian Networks, Relevance Networks, Graphical Gaussian models, Weight Matrices, Reverse Engineering Approach, Evolutionary Algorithms, Forward Modeling Approach, Deterministic models, Static models, Hybrid models, Stochastic models, Petri Nets, BioAmbients calculus and Differential Equations.Results:GRN and PPI methods have been already applied in various clinical processes with potential positive results, establishing promising diagnostic tools.Conclusion:In literature many stochastic algorithms are focused in the simulation, analysis and visualization of the various biological networks and their dynamics interactions, which are referred and described in depth in this review paper.

scholarly journals Genetic and Molecular Characterization of the Caenorhabditis elegans Gene, mel-26, a Postmeiotic Negative Regulator of MEI-1, a Meiotic-Specific Spindle Component

Genetics ◽  
1998 ◽  
Vol 150 (1) ◽  
pp. 119-128
Author(s):  
M Rhys Dow ◽  
Paul E Mains
Keyword(s):  
Caenorhabditis Elegans ◽  
Protein Interactions ◽  
Negative Regulator ◽  
Meiotic Spindle ◽  
Loss Of Function ◽  
Protein Protein Interactions ◽  
Gain Of Function ◽  
Recessive Mutations ◽  
Female Germline

Abstract We have previously described the gene mei-1, which encodes an essential component of the Caenorhabditis elegans meiotic spindle. When ectopically expressed after the completion of meiosis, mei-1 protein disrupts the function of the mitotic cleavage spindles. In this article, we describe the cloning and the further genetic characterization of mel-26, a postmeiotic negative regulator of mei-1. mel-26 was originally identified by a gain-of-function mutation. We have reverted this mutation to a loss-of-function allele, which has recessive phenotypes identical to the dominant defects of its gain-of-function parent. Both the dominant and recessive mutations of mel-26 result in mei-1 protein ectopically localized in mitotic spindles and centrosomes, leading to small and misoriented cleavage spindles. The loss-of-function mutation was used to clone mel-26 by transformation rescue. As suggested by genetic results indicating that mel-26 is required only maternally, mel-26 mRNA was expressed predominantly in the female germline. The gene encodes a protein that includes the BTB motif, which is thought to play a role in protein-protein interactions.

Proteomic Characterization of Protein-Protein Interactions

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Veenstra TD ◽  
Keyword(s):  
Protein Interactions ◽  
Disease Diagnosis ◽  
Cell System ◽  
Protein Protein Interactions ◽  
Novel Technologies ◽  
Cell Functions ◽  
Single Protein ◽  
A Cell ◽  
Molecular Components

Identifying all the molecular components within a living cell is the first step into understanding how it functions. To further understand how a cell functions requires identifying the interactions that occur between these components. This fact is especially relevant for proteins. No protein within a human cell functions on its own without interacting with another biomolecule - usually another protein. While Protein-Protein Interactions (PPI) have historically been determined by examining a single protein per study, novel technologies developed over the past couple of decades are enabling high-throughput methods that aim to describe entire protein networks within cells. In this review, some of the technologies that have led to these developments are described along with applications of these techniques. Ultimately the goal of these technologies is to map out the entire circuitry of PPI within human cells to be able to predict the global consequences of perturbations to the cell system. This predictive capability will have major impacts on the future of both disease diagnosis and treatment.

scholarly journals Characterization of major chromatin assembly proteins in tetrahymena thermophile using proeomic and molecular evolutionary analyses

2021 ◽  
Author(s):  
Syed N Shah
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Affinity Purification ◽  
Regulation Of Gene Expression ◽  
Chromatin Assembly ◽  
Histone Chaperones ◽  
Protein Protein Interactions ◽  
Selective Forces ◽  
Assembly Proteins

Histones H3/H4 are deposited onto DNA in a replication-dependent or independent fashion by the CAF1 and HIRA protein complexes. Despite the identification of these protein complexes, mechanistic details remain unclear. Recently, we showed that in T. thermophila histone chaperones Nrp1, Asf1 and the Impβ6 importin function together to transport newly synthesized H3/H4 from the cytoplasm to the nucleus. To characterize chromatin assembly proteins in T.thermophila, I used affinity purification combined with mass spectrometry to identify protein-protein interactions of Nrp1, Cac2 subunit of CAF1, HIRA and histone modifying Hat1-complex in T. thermophila. I found that the three-subunit T.thermophila CAF1 complex interacts with Casein Kinase 2 (CKII), possibly accounting for previously reported human CAF1phosphorylation. I also found that Hat2 subunit of HAT1 complex is also shared by CAF1 complex as its Cac3 subunit. This suggests that Hat2/Cac3 might exist in two separate pools of protein complexes. Remarkably, proteomic analysis of Hat2/Cac3 in turn revealed that it forms several complexes with other proteins including SIN3, RXT3, LIN9 and TESMIN, all of which have known roles in the regulation of gene expression. Finally, I asked how selective forces might have impacted on the function of proteins involved in H3/H4 transport. Focusing on NASP which possesses several TPR motifs, I showed that its protein-protein interactions are conserved in T. thermophila. Using molecular evolutionary methods I show that different TPRs in NASP evolve at different rates possibly accounting for the functional diversity observed among different family members.

scholarly journals Characterization of COMMD protein–protein interactions in NF-κB signalling

2006 ◽  
Vol 398 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Prim de Bie ◽  
Bart van de Sluis ◽  
Ezra Burstein ◽  
Karen J. Duran ◽  
Ruud Berger ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Copper Metabolism ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Protein Family ◽  
Amino Acid Residues ◽  
Protein Protein Interactions ◽  
Necrosis Factor

COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-inhibiting proteins, characterized by the presence of the COMM domain. In the present paper, we report detailed investigation of the role of this protein family, and specifically the role of the COMM domain, in NF-κB signalling through characterization of protein–protein interactions involving COMMD proteins. The small ubiquitously expressed COMMD6 consists primarily of the COMM domain. Therefore COMMD1 and COMMD6 were analysed further as prototype members of the COMMD protein family. Using specific antisera, interaction between endogenous COMMD1 and COMMD6 is described. This interaction was verified by independent techniques, appeared to be direct and could be detected throughout the whole cell, including the nucleus. Both proteins inhibit TNF (tumour necrosis factor)-induced NF-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB in an overlapping, but not completely similar, manner. Taken together, these data support the significance of COMMD protein–protein interactions and provide new mechanistic insight into the function of this protein family in NF-κB signalling.

scholarly journals Aspartic Acid Isomerization Characterized by High Definition Mass Spectrometry Significantly Alters the Bioactivity of a Novel Toxin from Poecilotheria

Toxins ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 207 ◽  
Author(s):  
Stephen R. Johnson ◽  
Hillary G. Rikli
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Ion Mobility ◽  
Protein Protein Interactions ◽  
High Definition ◽  
Vast Number ◽  
Post Translational Modifications ◽  
C Terminus ◽  
Acid Isomerization

Research in toxinology has created a pharmacological paradox. With an estimated 220,000 venomous animals worldwide, the study of peptidyl toxins provides a vast number of effector molecules. However, due to the complexity of the protein-protein interactions, there are fewer than ten venom-derived molecules on the market. Structural characterization and identification of post-translational modifications are essential to develop biological lead structures into pharmaceuticals. Utilizing advancements in mass spectrometry, we have created a high definition approach that fuses conventional high-resolution MS-MS with ion mobility spectrometry (HDMSE) to elucidate these primary structure characteristics. We investigated venom from ten species of “tiger” spider (Genus: Poecilotheria) and discovered they contain isobaric conformers originating from non-enzymatic Asp isomerization. One conformer pair conserved in five of ten species examined, denominated PcaTX-1a and PcaTX-1b, was found to be a 36-residue peptide with a cysteine knot, an amidated C-terminus, and isoAsp33Asp substitution. Although the isomerization of Asp has been implicated in many pathologies, this is the first characterization of Asp isomerization in a toxin and demonstrates the isomerized product’s diminished physiological effects. This study establishes the value of a HDMSE approach to toxin screening and characterization.

Sign in / Sign up

Export Citation Format

Share Document