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Protein Science : a Publication of the... Sep 2018The beta pore-forming proteins (β-PFPs) are a large class of polypeptides that are produced by all Kingdoms of life to contribute to their species' own survival. Pore... (Review)
Review
The beta pore-forming proteins (β-PFPs) are a large class of polypeptides that are produced by all Kingdoms of life to contribute to their species' own survival. Pore assembly is a sophisticated multi-step process that includes receptor/membrane recognition and oligomerization events, and is ensued by large-scale structural rearrangements, which facilitate maturation of a prepore into a functional membrane spanning pore. A full understanding of pore formation, assembly, and maturation has traditionally been hindered by a lack of structural data; particularly for assemblies representing differing conformations of functional pores. However, recent advancements in cryo-electron microscopy (cryo-EM) techniques have provided the opportunity to delineate the structures of such flexible complexes, and in different states, to near-atomic resolution. In this review, we place a particular emphasis on the use of cryo-EM to uncover the mechanistic details including architecture, activation, and maturation for some of the prominent members of this family.
Topics: Cryoelectron Microscopy; Humans; Pore Forming Cytotoxic Proteins; Protein Conformation
PubMed: 30129169
DOI: 10.1002/pro.3454 -
Cells Oct 2021Two-pore-domain potassium (K-) channels conduct outward K currents that maintain the resting membrane potential and modulate action potential repolarization. Members of... (Review)
Review
Two-pore-domain potassium (K-) channels conduct outward K currents that maintain the resting membrane potential and modulate action potential repolarization. Members of the K channel family are widely expressed among different human cell types and organs where they were shown to regulate important physiological processes. Their functional activity is controlled by a broad variety of different stimuli, like pH level, temperature, and mechanical stress but also by the presence of lipids or pharmacological agents. In patients suffering from cardiovascular diseases, alterations in K-channel expression and function have been observed, suggesting functional significance and a potential therapeutic role of these ion channels. For example, upregulation of atrial specific K3.1 (TASK-1) currents in atrial fibrillation (AF) patients was shown to contribute to atrial action potential duration shortening, a key feature of AF-associated atrial electrical remodelling. Therefore, targeting K3.1 (TASK-1) channels might constitute an intriguing strategy for AF treatment. Further, mechanoactive K2.1 (TREK-1) currents have been implicated in the development of cardiac hypertrophy, cardiac fibrosis and heart failure. Cardiovascular expression of other K channels has been described, functional evidence in cardiac tissue however remains sparse. In the present review, expression, function, and regulation of cardiovascular K channels are summarized and compared among different species. Remodelling patterns, observed in disease models are discussed and compared to findings from clinical patients to assess the therapeutic potential of K channels.
Topics: Animals; Atrial Remodeling; Cardiovascular Diseases; Gene Expression Regulation; Humans; Myocardium; Potassium Channels, Tandem Pore Domain
PubMed: 34831137
DOI: 10.3390/cells10112914 -
Seminars in Cell & Developmental Biology Aug 2017The study of the Nuclear Pore Complex (NPC), the proteins that compose it (nucleoporins), and the nucleocytoplasmic transport that it controls have revealed an... (Review)
Review
The study of the Nuclear Pore Complex (NPC), the proteins that compose it (nucleoporins), and the nucleocytoplasmic transport that it controls have revealed an unexpected layer to pathogenic disease onset and progression. Recent advances in the study of the regulation of NPC composition and function suggest that the precise control of this structure is necessary to prevent diseases from arising or progressing. Here we discuss the role of nucleoporins in a diverse set of diseases, many of which directly or indirectly increase in occurrence and severity as we age, and often shorten the human lifespan. NPC biology has been shown to play a direct role in these diseases and therefore in the process of healthy aging.
Topics: Aging; Disease; Humans; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 28506892
DOI: 10.1016/j.semcdb.2017.05.006 -
Molecular Cell Dec 2021A cryo-electron tomography structure of the human nuclear pore complex captured in cellulo by Schuller, Wojtynek et al. reveals that nuclear envelope tension expands...
A cryo-electron tomography structure of the human nuclear pore complex captured in cellulo by Schuller, Wojtynek et al. reveals that nuclear envelope tension expands the central transport channel and imposes asymmetry in the pore membrane.
Topics: Humans; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 34919818
DOI: 10.1016/j.molcel.2021.11.029 -
Anaerobe Dec 2014Pore formation is a common mechanism of action for many bacterial toxins. More than one third of clostridial toxins are pore-forming toxins (PFTs) belonging to the... (Review)
Review
Pore formation is a common mechanism of action for many bacterial toxins. More than one third of clostridial toxins are pore-forming toxins (PFTs) belonging to the β-PFT class. They are secreted as soluble monomers rich in β-strands, which recognize a specific receptor on target cells and assemble in oligomers. Then, they undergo a conformational change leading to the formation of a β-barrel, which inserts into the lipid bilayer forming functional pore. According to their structure, clostridial β-PFTs are divided into several families. Clostridial cholesterol-dependent cytolysins form large pores, which disrupt the plasma membrane integrity. They are potent virulence factors mainly involved in myonecrosis. Clostridial heptameric β-PFTs (aerolysin family and staphylococcal α-hemolysin family) induce small pores which trigger signaling cascades leading to different cell responses according to the cell types and toxins. They are mainly responsible for intestinal diseases, like necrotic enteritis, or systemic diseases/toxic shock from intestinal origin. Clostridial intracellularly active toxins exploit pore formation through the endosomal membrane to translocate the enzymatic component or domain into the cytosol. Single chain protein toxins, like botulinum and tetanus neurotoxins, use hydrophobic α-helices to form pores, whereas clostridial binary toxins encompass binding components, which are structurally and functionally related to β-PFTs, but which have acquired the specific activity to internalize their corresponding enzymatic components. Structural analysis suggests that β-PFTs and binding components share a common evolutionary origin.
Topics: Bacterial Toxins; Cell Membrane; Clostridium; Evolution, Molecular; Genetic Variation; Intracellular Membranes; Pore Forming Cytotoxic Proteins; Virulence Factors
PubMed: 24952276
DOI: 10.1016/j.anaerobe.2014.05.014 -
ACS Omega May 2022We have simulated pore formation and shape control of lotus aluminum by the phase-field method. The simulated material, lotus aluminum, contains anisotropic internal...
We have simulated pore formation and shape control of lotus aluminum by the phase-field method. The simulated material, lotus aluminum, contains anisotropic internal pores, and it is produced by the continuous casting method in a hydrogen atmosphere. Since it is known experimentally that the pore shape of lotus aluminum changes with the pull-out speed, the simulation varied the movement speed of the temperature gradient zone (equivalent to the pull-out speed in the continuous casting method) by proportional differential (PD) control with the pore width as the target value. As a result, a simple PD control ensured the pores closed during the growth process. To keep the pore growth linear, we found that a lower limit of the interface temperature should be set and the temperature gradient zone should be stopped below this lower limit. However, a problem occurred in the pore shape. To mitigate necking of the pore, PD control was done only when the pore width became larger than the target value under the conditions such that the pore expanded easily (i.e., the pull-out movement was stopped for a certain time immediately after nucleation and the initial speed of the temperature gradient zone was decreased). Then, we found the best condition to achieve linear pore growth without necking. Under the same condition, we simulated multiple pore growths by allowing multiple nucleations. As a result, we observed that although the shape control was applied only to a certain single pore, the other pores also grew linearly if the timing of their nucleation was close to that of the target pore.
PubMed: 35557706
DOI: 10.1021/acsomega.2c00733 -
The New Phytologist Jul 2018Contents Summary 25 I Introduction 25 II. Structural organization of the NPC 26 III. The role of NPCs in immune signaling 26 IV. The role of NPCs in hormone signaling 28... (Review)
Review
Contents Summary 25 I Introduction 25 II. Structural organization of the NPC 26 III. The role of NPCs in immune signaling 26 IV. The role of NPCs in hormone signaling 28 V. Conclusions 29 Acknowledgements 29 References 29 SUMMARY: Nuclear pore complexes (NPCs) are fundamental components of the eukaryotic cell. They perforate the nuclear envelope and serve as highly selective transport gates that enable bi-directional macromolecule exchange between the nucleus and cytoplasm. Recent studies illustrate that the NPC is not a static structural channel but a flexible environment and strategic player during nuclear signaling. The constitutional and conformational dynamics of the NPC allow it to tailor nucleocytoplasmic transport activities and define specific signaling output in response to various cellular and environmental cues. In this Insight, we review the roles of NPC constituents in immune activation and hormone signaling in plants, and discuss the possible role of the NPC as a legitimate platform for regulating cell signaling.
Topics: Active Transport, Cell Nucleus; Cell Nucleus; Cytoplasm; Nuclear Envelope; Nuclear Pore; Nuclear Pore Complex Proteins; Plant Growth Regulators; Plant Immunity; Plants; Signal Transduction
PubMed: 28858378
DOI: 10.1111/nph.14756 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Dec 2023To solve the current problems of loosening and dislodging caused by the high elastic modulus of solid implants, we attempted to study a gradient porous dental implant...
OBJECTIVES
To solve the current problems of loosening and dislodging caused by the high elastic modulus of solid implants, we attempted to study a gradient porous dental implant that can lower the stress concentration and reduce the elastic modulus.
METHODS
SolidWorks software was utilized to design the abutment and mechanical structure of the gradient porous implant. The mechanical properties of the gradient porous implant were evaluated by an orthogonal experimental design from four aspects: pore shape, pore diameter, porous layer height, and circumferential distribution. ANSYS software was used to evaluate the distribution of Von-Mises stress in the implant and its surrounding bone tissues under different structural combination parameters to derive the optimal combination of gradient porous implant parameters.
RESULTS
The effects of the four factors, namely, pore shape, pore diameter, porous layer height and pore distribution, on the maximum Von-Mises stress on the implant were as follows. As the pore shape became smaller and the circumferential distribution decreased, the Von-Mises stress decreased significantly. The pore diameter went from 500 μm to 600 μm and then to 700 μm. The Von-Mises stress decreased and then increased. It increased with the increase in the height of the porous layer.
CONCLUSIONS
The final optimal combination of parameters for the gradient porous implant was as follows: square pore shape, pore diameter of 600 μm, porous layer height of 3 mm, and quadratic step in pore distribution.
Topics: Dental Implants; Dental Prosthesis Design; Porosity; Finite Element Analysis; Dental Stress Analysis; Biomechanical Phenomena; Stress, Mechanical
PubMed: 38597029
DOI: 10.7518/hxkq.2023.2023188 -
Current Biology : CB Jan 2005A new study shows that the filamentous fungus, Aspergillus nidulans, which has a closed mitosis, does not maintain a continuous permeability barrier during mitosis. This... (Review)
Review
A new study shows that the filamentous fungus, Aspergillus nidulans, which has a closed mitosis, does not maintain a continuous permeability barrier during mitosis. This work challenges current views of the differences between closed and open mitosis and has implications for understanding mitotic specific changes in the nuclear pore complex and Ran GTPase system in lower eukaryotes.
Topics: Aspergillus nidulans; GTP Phosphohydrolases; Mitosis; Nuclear Pore; Permeability; ran GTP-Binding Protein
PubMed: 15649347
DOI: 10.1016/j.cub.2004.12.015 -
Nucleus (Austin, Tex.) 2015Nuclear pore complexes (NPCs) mediate molecular transport between the nucleus and cytoplasm in eukaryotic cells. Tethered within each NPC lie numerous intrinsically... (Review)
Review
Nuclear pore complexes (NPCs) mediate molecular transport between the nucleus and cytoplasm in eukaryotic cells. Tethered within each NPC lie numerous intrinsically disordered proteins known as FG nucleoporins (FG Nups) that are central to this process. Over two decades of investigation has converged on a view that a barrier mechanism consisting of FG Nups rejects non-specific macromolecules while promoting the speed and selectivity of karyopherin (Kaps) receptors (and their cargoes). Yet, the number of NPCs in the cell is exceedingly small compared to the number of Kaps, so that in fact there is a high likelihood the pores are always populated by Kaps. Here, we contemplate a view where Kaps actively participate in regulating the selectivity and speed of transport through NPCs. This so-called "Kap-centric" control of the NPC accounts for Kaps as essential barrier reinforcements that play a prerequisite role in facilitating fast transport kinetics. Importantly, Kap-centric control reconciles both mechanistic and kinetic requirements of the NPC, and in so doing potentially resolves incoherent aspects of FG-centric models. On this basis, we surmise that Kaps prime the NPC for nucleocytoplasmic transport by fine-tuning the NPC microenvironment according to the functional needs of the cell.
Topics: Animals; Biophysical Phenomena; Cellular Microenvironment; Humans; Karyopherins; Nuclear Pore; Nuclear Pore Complex Proteins
PubMed: 26338152
DOI: 10.1080/19491034.2015.1090061