Putting the actin cytoskeleton into perspective: pathophysiology of ischemic alterations

1997 ◽  
Vol 272 (4) ◽  
pp. F430-F433 ◽  
Author(s):  
B. A. Molitoris
Keyword(s):  
Actin Cytoskeleton ◽  
Protein Interactions ◽  
Cell Injury ◽  
Surface Membrane ◽  
Effector Proteins ◽  
Cellular Migration ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Cellular Processes ◽  
And Function

The actin cytoskeleton plays an ever-increasingly understood role in mediating a myriad of processes necessary for cellular structure and function. New and exciting information regarding the dynamic aspects of the actin cytoskeleton and its intracellular regulation are unfolding at a rapid rate. Actin cytoskeletal-surface membrane interactions mediating such diverse cellular events as cell polarity, endocytosis, exocytosis, cell division, cellular migration, cell adhesion, signal transduction, and ion channel activity are part of an ever-growing list of cellular processes dependent on precise actin polarization and regulation of assembly and disassembly. The purpose of this review is to highlight recent advances in the understanding of actin cytoskeleton-mediated cellular processes, to provide a framework that interrelates the complex protein-protein interactions necessary for localization, regulation, and mediation of these essential cellular functions, and to outline the role of actin effector proteins in the pathophysiology of ischemic cell injury.

scholarly journals Label-free methods for optical in vitro characterization of protein–protein interactions

2021 ◽  
Author(s):  
Fabian Soltermann ◽  
Weston B. Struwe ◽  
Philipp Kukura
Keyword(s):  
Protein Interactions ◽  
Label Free ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
P Protein ◽  
In Vitro Characterization ◽  
And Function

Protein–protein interactions are involved in the regulation and function of the majority of cellular processes.

scholarly journals MOB (Mps one Binder) Proteins in the Hippo Pathway and Cancer

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 569 ◽  
Author(s):  
Gundogdu ◽  
Hergovich
Keyword(s):  
Protein Interactions ◽  
Hippo Pathway ◽  
Tissue Growth ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Signal Transducers ◽  
Cellular Processes ◽  
Disease Spectrum ◽  
Monopolar Spindle ◽  
Regeneration Pathway

The family of MOBs (monopolar spindle-one-binder proteins) is highly conserved in the eukaryotic kingdom. MOBs represent globular scaffold proteins without any known enzymatic activities. They can act as signal transducers in essential intracellular pathways. MOBs have diverse cancer-associated cellular functions through regulatory interactions with members of the NDR/LATS kinase family. By forming additional complexes with serine/threonine protein kinases of the germinal centre kinase families, other enzymes and scaffolding factors, MOBs appear to be linked to an even broader disease spectrum. Here, we review our current understanding of this emerging protein family, with emphases on post-translational modifications, protein-protein interactions, and cellular processes that are possibly linked to cancer and other diseases. In particular, we summarise the roles of MOBs as core components of the Hippo tissue growth and regeneration pathway.

scholarly journals Structural basis for the dimerization of Gemin5 and its role in protein recruitment and translation control

2019 ◽  
Vol 48 (2) ◽  
pp. 788-801 ◽  
Author(s):  
María Moreno-Morcillo ◽  
Rosario Francisco-Velilla ◽  
Azman Embarc-Buh ◽  
Javier Fernández-Chamorro ◽  
Santiago Ramón-Maiques ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Rna Binding ◽  
Structural Basis ◽  
Middle Region ◽  
Protein Protein Interactions ◽  
Translation Control ◽  
Dimerization Domain ◽  
Multifunctional Protein ◽  
Cellular Processes ◽  
And Function

Abstract In all organisms, a selected type of proteins accomplishes critical roles in cellular processes that govern gene expression. The multifunctional protein Gemin5 cooperates in translation control and ribosome binding, besides acting as the RNA-binding protein of the survival of motor neuron (SMN) complex. While these functions reside on distinct domains located at each end of the protein, the structure and function of the middle region remained unknown. Here, we solved the crystal structure of an extended tetratricopeptide (TPR)-like domain in human Gemin5 that self-assembles into a previously unknown canoe-shaped dimer. We further show that the dimerization module is functional in living cells driving the interaction between the viral-induced cleavage fragment p85 and the full-length Gemin5, which anchors splicing and translation members. Disruption of the dimerization surface by a point mutation in the TPR-like domain prevents this interaction and also abrogates translation enhancement induced by p85. The characterization of this unanticipated dimerization domain provides the structural basis for a role of the middle region of Gemin5 as a central hub for protein-protein interactions.

Ca2+-Activated K+ Channels: From Protein Complexes to Function

2010 ◽  
Vol 90 (4) ◽  
pp. 1437-1459 ◽  
Author(s):  
Henrike Berkefeld ◽  
Bernd Fakler ◽  
Uwe Schulte
Keyword(s):  
Protein Interactions ◽  
Muscle Tone ◽  
Protein Complexes ◽  
Neuronal Firing ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
And Function ◽  
And Control ◽  
Proteomic Research ◽  
Partner Proteins

Molecular research on ion channels has demonstrated that many of these integral membrane proteins associate with partner proteins, often versatile in their function, or even assemble into stable macromolecular complexes that ensure specificity and proper rate of the channel-mediated signal transduction. Calcium-activated potassium (KCa) channels that link excitability and intracellular calcium concentration are responsible for a wide variety of cellular processes ranging from regulation of smooth muscle tone to modulation of neurotransmission and control of neuronal firing pattern. Most of these functions are brought about by interaction of the channels' pore-forming subunits with distinct partner proteins. In this review we summarize recent insights into protein complexes associated with KCa channels as revealed by proteomic research and discuss the results available on structure and function of these complexes and on the underlying protein-protein interactions. Finally, the results are related to their significance for the function of KCa channels under cellular conditions.

scholarly journals Global mapping of Salmonella enterica-host protein-protein interactions during infection

2020 ◽  
Author(s):  
Philipp Walch ◽  
Joel Selkrig ◽  
Leigh A. Knodler ◽  
Mandy Rettel ◽  
Frank Stein ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Salmonella Enterica ◽  
Affinity Purification ◽  
Cell Types ◽  
Effector Proteins ◽  
Host Protein ◽  
Host Cells ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Serovar Typhimurium

SummaryIntracellular bacterial pathogens inject effector proteins into host cells to hijack diverse cellular processes and promote their survival and proliferation. To systematically map effector-host protein-protein interactions (PPIs) during infection, we generated a library of 32 Salmonella enterica serovar Typhimurium (STm) strains expressing chromosomally encoded affinity-tagged effector proteins, and quantified PPIs in macrophages and epithelial cells by Affinity-Purification Quantitative Mass-Spectrometry. Thereby, we identified 25 previously described and 421 novel effector-host PPIs. While effectors converged on the same host cellular processes, most had multiple targets, which often differed between cell types. Using reciprocal co-immunoprecipitations, we validated 13 out of 22 new PPIs. We then used this host-pathogen physical interactome resource to demonstrate that SseJ and SseL collaborate in redirecting cholesterol to the Salmonella Containing Vacuole (SCV) via NPC1, PipB directly recruits the organelle contact site protein PDZD8 to the SCV, and SteC promotes actin bundling by directly phosphorylating formin-like proteins.

scholarly journals Mimicking Strategy for Protein–Protein Interaction Inhibitor Discovery by Virtual Screening

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4428 ◽  
Author(s):  
Ke-Jia Wu ◽  
Pui-Man Lei ◽  
Hao Liu ◽  
Chun Wu ◽  
Chung-Hang Leung ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Promising Strategy ◽  
Protein Partners ◽  
Inhibitor Discovery ◽  
And Function

As protein–protein interactions (PPIs) are highly involved in most cellular processes, the discovery of PPI inhibitors that mimic the structure of the natural protein partners is a promising strategy toward the discovery of PPI inhibitors. In this review, we discuss recent advances in the application of virtual screening for identifying mimics of protein partners. The classification and function of the mimicking protein partner inhibitor discovery by virtual screening are described. We anticipate that this review would be of interest to medicinal chemists and chemical biologists working in the field of protein–protein interaction inhibitors or probes.

scholarly journals Mechanisms of the 14-3-3 Protein Function: Regulation of Protein Function Through Conformational Modulation

2014 ◽  
pp. S155-S164 ◽  
Author(s):  
V. OBSILOVA ◽  
M. KOPECKA ◽  
D. KOSEK ◽  
M. KACIROVA ◽  
S. KYLAROVA ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Specific Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Cellular Processes ◽  
Binding Partners ◽  
Regulatory Functions

Many aspects of protein function regulation require specific protein-protein interactions to carry out the exact biochemical and cellular functions. The highly conserved members of the 14-3-3 protein family mediate such interactions and through binding to hundreds of other proteins provide multitude of regulatory functions, thus playing key roles in many cellular processes. The 14-3-3 protein binding can affect the function of the target protein in many ways including the modulation of its enzyme activity, its subcellular localization, its structure and stability, or its molecular interactions. In this minireview, we focus on mechanisms of the 14-3-3 protein-dependent regulation of three important 14-3-3 binding partners: yeast neutral trehalase Nth1, regulator of G-protein signaling 3 (RGS3), and phosducin.

scholarly journals Bend, Push, Stretch: Remarkable Structure and Mechanics of Single Intermediate Filaments and Meshworks

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1960
Author(s):  
K. Tanuj Sapra ◽  
Ohad Medalia
Keyword(s):  
Intermediate Filaments ◽  
Eukaryotic Cell ◽  
Coiled Coils ◽  
Cellular Functions ◽  
Mechanical Pressure ◽  
Mechanical Feature ◽  
Cellular Processes ◽  
Nuclear Lamins ◽  
Filament Networks ◽  
And Function

The cytoskeleton of the eukaryotic cell provides a structural and functional scaffold enabling biochemical and cellular functions. While actin and microtubules form the main framework of the cell, intermediate filament networks provide unique mechanical properties that increase the resilience of both the cytoplasm and the nucleus, thereby maintaining cellular function while under mechanical pressure. Intermediate filaments (IFs) are imperative to a plethora of regulatory and signaling functions in mechanotransduction. Mutations in all types of IF proteins are known to affect the architectural integrity and function of cellular processes, leading to debilitating diseases. The basic building block of all IFs are elongated α-helical coiled-coils that assemble hierarchically into complex meshworks. A remarkable mechanical feature of IFs is the capability of coiled-coils to metamorphize into β-sheets under stress, making them one of the strongest and most resilient mechanical entities in nature. Here, we discuss structural and mechanical aspects of IFs with a focus on nuclear lamins and vimentin.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

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.

Sign in / Sign up

Export Citation Format

Share Document