scholarly journals Protein–protein interactions in intracellular Ca2+-release channel function

1999 ◽  
Vol 337 (3) ◽  
pp. 345-361 ◽  
Author(s):  
John J. MACKRILL
Keyword(s):  
Protein Interactions ◽  
Ryanodine Receptors ◽  
Accessory Proteins ◽  
Protein Protein Interactions ◽  
Release Channel ◽  
Specific Effects ◽  
Complex Protein ◽  
A Cell ◽  
And Function ◽  
Opposing Effects

Release of Ca2+ ions from intracellular stores can occur via two classes of Ca2+-release channel (CRC) protein, the inositol 1,4,5-trisphosphate receptors (InsP3Rs) and the ryanodine receptors (RyRs). Multiple isoforms and subtypes of each CRC class display distinct but overlapping distributions within mammalian tissues. InsP3Rs and RyRs interact with a plethora of accessory proteins which modulate the activity of their intrinsic channels. Although many aspects of CRC structure and function have been reviewed in recent years, the properties of proteins with which they interact has not been comprehensively surveyed, despite extensive current research on the roles of these modulators. The aim of this article is to review the regulation of CRC activity by accessory proteins and, wherever possible, to outline the structural details of such interactions. The CRCs are large transmembrane proteins, with the bulk of their structure located cytoplasmically. Intra- and inter-complex protein–protein interactions between these cytoplasmic domains also regulate CRC function. Some accessory proteins modulate channel activity of all CRC subtypes characterized, whereas other have class- or even isoform-specific effects. Certain accessory proteins exert both direct and indirect forms of regulation on CRCs, occasionally with opposing effects. Others are themselves modulated by changes in Ca2+ concentration, thereby participating in feedback mechanisms acting on InsP3R and RyR activity. CRCs are therefore capable of integrating numerous signalling events within a cell by virtue of such protein–protein interactions. Consequently, the functional properties of InsP3Rs and RyRs within particular cells and subcellular domains are ‘customized ’ by the accessory proteins present.

scholarly journals Evolutionary design principles in metabolism

2019 ◽  
Vol 286 (1898) ◽  
pp. 20190098 ◽  
Author(s):  
Gayathri Sambamoorthy ◽  
Himanshu Sinha ◽  
Karthik Raman
Keyword(s):  
Protein Interactions ◽  
Metabolic Networks ◽  
Design Principles ◽  
Dynamic Environments ◽  
Evolutionary Design ◽  
Protein Protein Interactions ◽  
Flux Coupling ◽  
A Cell ◽  
And Function ◽  
Novel Design

Microorganisms are ubiquitous and adapt to various dynamic environments to sustain growth. These adaptations accumulate, generating new traits forming the basis of evolution. Organisms adapt at various levels, such as gene regulation, signalling, protein–protein interactions and metabolism. Of these, metabolism forms the integral core of an organism for maintaining the growth and function of a cell. Therefore, studying adaptations in metabolic networks is crucial to understand the emergence of novel metabolic capabilities. Metabolic networks, composed of enzyme-catalysed reactions, exhibit certain repeating paradigms or design principles that arise out of different selection pressures. In this review, we discuss the design principles that are known to exist in metabolic networks, such as functional redundancy, modularity, flux coupling and exaptations. We elaborate on the studies that have helped gain insights highlighting the interplay of these design principles and adaptation. Further, we discuss how evolution plays a role in exploiting such paradigms to enhance the robustness of organisms. Looking forward, we predict that with the availability of ever-increasing numbers of bacterial, archaeal and eukaryotic genomic sequences, novel design principles will be identified, expanding our understanding of these paradigms shaped by varied evolutionary processes.

scholarly journals Complex Protein Interactions within the Human Polyadenylation Machinery Identify a Novel Component

2000 ◽  
Vol 20 (5) ◽  
pp. 1515-1525 ◽  
Author(s):  
Yoshio Takagaki ◽  
James L. Manley
Keyword(s):  
Protein Interactions ◽  
Rna Binding ◽  
Small Region ◽  
Protein Protein Interactions ◽  
Significant Similarity ◽  
Rich Domain ◽  
Complex Protein ◽  
Self Association ◽  
And Function ◽  
Cleavage Stimulation Factor

ABSTRACT Polyadenylation of mRNA precursors is a two-step reaction requiring multiple protein factors. Cleavage stimulation factor (CstF) is a heterotrimer necessary for the first step, endonucleolytic cleavage, and it plays an important role in determining the efficiency of polyadenylation. Although a considerable amount is known about the RNA binding properties of CstF, the protein-protein interactions required for its assembly and function are poorly understood. We therefore first identified regions of the CstF subunits, CstF-77, CstF-64, and CstF-50, required for interaction with each other. Unexpectedly, small regions of two of the subunits participate in multiple interactions. In CstF-77, a proline-rich domain is necessary not only for binding both other subunits but also for self-association, an interaction consistent with genetic studies in Drosophila. In CstF-64, a small region, highly conserved in metazoa, is responsible for interactions with two proteins, CstF-77 and symplekin, a nuclear protein of previously unknown function. Intriguingly, symplekin has significant similarity to a yeast protein, PTA1, that is a component of the yeast polyadenylation machinery. We show that multiple factors, including CstF, cleavage-polyadenylation specificity factor, and symplekin, can be isolated from cells as part of a large complex. These and other data suggest that symplekin may function in assembly of the polyadenylation machinery.

scholarly journals Transactivation Functions of the N-Terminal Domains of Nuclear Hormone Receptors: Protein Folding and Coactivator Interactions

2003 ◽  
Vol 17 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raj Kumar ◽  
E. Brad Thompson
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptor ◽  
Binding Domain ◽  
Dna Binding Domain ◽  
Protein Protein Interactions ◽  
Carboxy Terminal ◽  
And Function ◽  
Terminal Domains

Abstract The N-terminal domains (NTDs) of many members of the nuclear hormone receptor (NHR) family contain potent transcription-activating functions (AFs). Knowledge of the mechanisms of action of the NTD AFs has lagged, compared with that concerning other important domains of the NHRs. In part, this is because the NTD AFs appear to be unfolded when expressed as recombinant proteins. Recent studies have begun to shed light on the structure and function of the NTD AFs. Recombinant NTD AFs can be made to fold by application of certain osmolytes or when expressed in conjunction with a DNA-binding domain by binding that DNA-binding domain to a DNA response element. The sequence of the DNA binding site may affect the functional state of the AFs domain. If properly folded, NTD AFs can bind certain cofactors and primary transcription factors. Through these, and/or by direct interactions, the NTD AFs may interact with the AF2 domain in the ligand binding, carboxy-terminal portion of the NHRs. We propose models for the folding of the NTD AFs and their 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 Multi-Omics Analysis Identifying Key Biomarkers in Ovarian Cancer

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482097667
Author(s):  
Ju-Yueh Li ◽  
Chia-Jung Li ◽  
Li-Te Lin ◽  
Kuan-Hao Tsui
Keyword(s):  
Ovarian Cancer ◽  
Protein Interactions ◽  
Malignant Tumors ◽  
Single Gene ◽  
Protein Protein Interactions ◽  
Normal Tissues ◽  
Human Protein Atlas ◽  
Copy Number Changes ◽  
And Function ◽  
Cancer Tissues

Ovarian cancer is one of the most common malignant tumors. Here, we aimed to study the expression and function of the CREB1 gene in ovarian cancer via the bioinformatic analyses of multiple databases. Previously, the prognosis of ovarian cancer was based on single-factor or single-gene studies. In this study, different bioinformatics tools (such as TCGA, GEPIA, UALCAN, MEXPRESS, and Metascape) have been used to assess the expression and prognostic value of the CREB1 gene. We used the Reactome and cBioPortal databases to identify and analyze CREB1 mutations, copy number changes, expression changes, and protein–protein interactions. By analyzing data on the CREB1 differential expression in ovarian cancer tissues and normal tissues from 12 studies collected from the “Human Protein Atlas” database, we found a significantly higher expression of CREB1 in normal ovarian tissues. Using this database, we collected information on the expression of 25 different CREB-related proteins, including TP53, AKT1, and AKT3. The enrichment of these factors depended on tumor metabolism, invasion, proliferation, and survival. Individualized tumors based on gene therapy related to prognosis have become a new possibility. In summary, we established a new type of prognostic gene profile for ovarian cancer using the tools of bioinformatics.

scholarly journals Mitochondria: Regulators of Cell Death and Survival

2002 ◽  
Vol 2 ◽  
pp. 1569-1578 ◽  
Author(s):  
David J. Granville ◽  
Roberta A. Gottlieb
Keyword(s):  
Cell Death ◽  
Conformational Changes ◽  
Protein Interactions ◽  
Apoptotic Cell ◽  
Critical Role ◽  
Death Process ◽  
Protein Protein Interactions ◽  
Ionic Changes ◽  
A Cell ◽  
Cyt C

The past 5 years has seen an intense surge in research devoted toward understanding the critical role of mitochondria in the regulation of cell death. Apoptosis can be initiated by a wide array of stimuli, inducing multiple signaling pathways that, for the most part, converge at the mitochondrion. Although classically considered the powerhouses of the cell, it is now understood that mitochondria are also “gatekeepers” that ultimately determine the fate of the cell. The mitochondrial decision as to whether a cell lives or dies is complex, involving protein-protein interactions, ionic changes, reactive oxygen species, and other mechanisms that require further elucidation. Once the death process is initiated, mitochondria undergo conformational changes, resulting in the release of cytochrome c (cyt c), caspases, endonucleases, and other factors leading to the onset and execution of apoptosis. The present review attempts to outline the complex milieu of events regulating the mitochondrial commitment to and processes involved in the implementation of the executioner phase of apoptotic cell death.

scholarly journals Properties of the phage-shock-protein (Psp) regulatory complex that govern signal transduction and induction of the Psp response in Escherichia coli

Microbiology ◽  
2010 ◽  
Vol 156 (10) ◽  
pp. 2920-2932 ◽  
Author(s):  
Goran Jovanovic ◽  
Christoph Engl ◽  
Antony J. Mayhew ◽  
Patricia C. Burrows ◽  
Martin Buck
Keyword(s):  
Escherichia Coli ◽  
Signal Transduction ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Negative Control ◽  
Stress Conditions ◽  
Bacterial Cells ◽  
Protein Protein Interactions ◽  
Regulatory Complex ◽  
And Function

The phage-shock-protein (Psp) response maintains the proton-motive force (pmf) under extracytoplasmic stress conditions that impair the inner membrane (IM) in bacterial cells. In Escherichia coli transcription of the pspABCDE and pspG genes requires activation of σ 54-RNA polymerase by the enhancer-binding protein PspF. A regulatory network comprising PspF–A–C–B–ArcB controls psp expression. One key regulatory point is the negative control of PspF imposed by its binding to PspA. It has been proposed that under stress conditions, the IM-bound sensors PspB and PspC receive and transduce the signal(s) to PspA via protein–protein interactions, resulting in the release of the PspA–PspF inhibitory complex and the consequent induction of psp. In this work we demonstrate that PspB self-associates and interacts with PspC via putative IM regions. We present evidence suggesting that PspC has two topologies and that conserved residue G48 and the putative leucine zipper motif are determinants required for PspA interaction and signal transduction upon stress. We also establish that PspC directly interacts with the effector PspG, and show that PspG self-associates. These results are discussed in the context of formation and function of the Psp regulatory complex.

scholarly journals A cell-penetrant lactam-stapled peptide for targeting eIF4E protein-protein interactions

2020 ◽  
Vol 205 ◽  
pp. 112655
Author(s):  
Erin E. Gallagher ◽  
Arya Menon ◽  
Alyah F. Chmiel ◽  
Kirsten Deprey ◽  
Joshua A. Kritzer ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Stapled Peptide ◽  
A Cell

scholarly journals Distinct activities of Scrib module proteins organize epithelial polarity

2020 ◽  
Vol 117 (21) ◽  
pp. 11531-11540 ◽  
Author(s):  
Mark J. Khoury ◽  
David Bilder
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Epithelial Polarity ◽  
Protein Protein Interactions ◽  
Kinase C ◽  
Mutual Antagonism ◽  
Discs Large ◽  
Lethal Giant Larvae ◽  
Epithelial Structure ◽  
And Function

A polarized architecture is central to both epithelial structure and function. In many cells, polarity involves mutual antagonism between the Par complex and the Scribble (Scrib) module. While molecular mechanisms underlying Par-mediated apical determination are well-understood, how Scrib module proteins specify the basolateral domain remains unknown. Here, we demonstrate dependent and independent activities of Scrib, Discs-large (Dlg), and Lethal giant larvae (Lgl) using theDrosophilafollicle epithelium. Our data support a linear hierarchy for localization, but rule out previously proposed protein–protein interactions as essential for polarization. Cortical recruitment of Scrib does not require palmitoylation or polar phospholipid binding but instead an independent cortically stabilizing activity of Dlg. Scrib and Dlg do not directly antagonize atypical protein kinase C (aPKC), but may instead restrict aPKC localization by enabling the aPKC-inhibiting activity of Lgl. Importantly, while Scrib, Dlg, and Lgl are each required, all three together are not sufficient to antagonize the Par complex. Our data demonstrate previously unappreciated diversity of function within the Scrib module and begin to define the elusive molecular functions of Scrib and Dlg.

scholarly journals The Maturation Pathway of Nickel Urease

Inorganics ◽  
2019 ◽  
Vol 7 (7) ◽  
pp. 85 ◽  
Author(s):  
Yap Shing Nim ◽  
Kam-Bo Wong
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Toxic Metal ◽  
Specific Protein ◽  
Accessory Proteins ◽  
Protein Protein Interactions ◽  
Nickel Ions ◽  
Hydrogenase Maturation ◽  
Maturation Factor

Maturation of urease involves post-translational insertion of nickel ions to form an active site with a carbamylated lysine ligand and is assisted by urease accessory proteins UreD, UreE, UreF and UreG. Here, we review our current understandings on how these urease accessory proteins facilitate the urease maturation. The urease maturation pathway involves the transfer of Ni2+ from UreE → UreG → UreF/UreD → urease. To avoid the release of the toxic metal to the cytoplasm, Ni2+ is transferred from one urease accessory protein to another through specific protein–protein interactions. One central theme depicts the role of guanosine triphosphate (GTP) binding/hydrolysis in regulating the binding/release of nickel ions and the formation of the protein complexes. The urease and [NiFe]-hydrogenase maturation pathways cross-talk with each other as UreE receives Ni2+ from hydrogenase maturation factor HypA. Finally, the druggability of the urease maturation pathway is reviewed.

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