Misplaced Pages

#244755

48-457: The process of ERAD can be divided into three steps: The recognition of misfolded or mutated proteins depends on the detection of substructures within proteins such as exposed hydrophobic regions, unpaired cysteine residues and immature glycans . In mammalian cells for example, there exists a mechanism called glycan processing. In this mechanism, the lectin -type chaperones calnexin / calreticulin (CNX/CRT) provide immature glycoproteins

96-633: A bulk material, through either coatings or surface treatments. That is to say, the presence of molecular species (usually organic) or structural features results in high contact angles of water. In recent years, rare earth oxides have been shown to possess intrinsic hydrophobicity. The intrinsic hydrophobicity of rare earth oxides depends on surface orientation and oxygen vacancy levels, and is naturally more robust than coatings or surface treatments, having potential applications in condensers and catalysts that can operate at high temperatures or corrosive environments. Hydrophobic concrete has been produced since

144-417: A challenge in large part due to the difficulty in establishing experimental conditions that can preserve the correct ( native ) conformation of the protein in isolation from its native environment. Membrane proteins perform a variety of functions vital to the survival of organisms: The localization of proteins in membranes can be predicted reliably using hydrophobicity analyses of protein sequences, i.e.

192-540: A gas. where θ can be measured using a contact angle goniometer . Wenzel determined that when the liquid is in intimate contact with a microstructured surface, θ will change to θ W* where r is the ratio of the actual area to the projected area. Wenzel's equation shows that microstructuring a surface amplifies the natural tendency of the surface. A hydrophobic surface (one that has an original contact angle greater than 90°) becomes more hydrophobic when microstructured – its new contact angle becomes greater than

240-399: A high contact angle . Examples of hydrophobic molecules include the alkanes , oils , fats , and greasy substances in general. Hydrophobic materials are used for oil removal from water, the management of oil spills , and chemical separation processes to remove non-polar substances from polar compounds. Hydrophobic is often used interchangeably with lipophilic , "fat-loving". However,

288-413: A higher entropic state which causes non-polar molecules to clump together to reduce the surface area exposed to water and decrease the entropy of the system. Thus, the two immiscible phases (hydrophilic vs. hydrophobic) will change so that their corresponding interfacial area will be minimal. This effect can be visualized in the phenomenon called phase separation. Superhydrophobic surfaces, such as

336-527: A permanent part of a cell membrane and can either penetrate the membrane ( transmembrane ) or associate with one or the other side of a membrane ( integral monotopic ). Peripheral membrane proteins are transiently associated with the cell membrane. Membrane proteins are common, and medically important—about a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs. Nonetheless, compared to other classes of proteins, determining membrane protein structures remains

384-479: A retrotranslocon or dislocon to transport substrates into the cytosol. Hrd1 is not required for all ERAD events, so it is likely that other proteins contribute to this process. For example, glycosylated substrates are recognized by the E3 Fbs2 lectin. Further, this translocation requires a driving force that determines the direction of transport. Since polyubiquitination is essential for the export of substrates , it

432-681: A surface having micrometer-sized features or particles ≤ 100 micrometers. The larger particles were observed to protect the smaller particles from mechanical abrasion. In recent research, superhydrophobicity has been reported by allowing alkylketene dimer (AKD) to solidify into a nanostructured fractal surface. Many papers have since presented fabrication methods for producing superhydrophobic surfaces including particle deposition, sol-gel techniques, plasma treatments, vapor deposition, and casting techniques. Current opportunity for research impact lies mainly in fundamental research and practical manufacturing. Debates have recently emerged concerning

480-586: A surface is easily washed away. Patterned superhydrophobic surfaces also have promise for lab-on-a-chip microfluidic devices and can drastically improve surface-based bioanalysis. In pharmaceuticals, hydrophobicity of pharmaceutical blends affects important quality attributes of final products, such as drug dissolution and hardness . Methods have been developed to measure the hydrophobicity of pharmaceutical materials. The development of hydrophobic passive daytime radiative cooling (PDRC) surfaces, whose effectiveness at solar reflectance and thermal emittance

528-410: Is a phenomenon that characterizes surface heterogeneity. When a pipette injects a liquid onto a solid, the liquid will form some contact angle. As the pipette injects more liquid, the droplet will increase in volume, the contact angle will increase, but its three-phase boundary will remain stationary until it suddenly advances outward. The contact angle the droplet had immediately before advancing outward

SECTION 10

#1732772769245

576-399: Is based on this principle. Inspired by it , many functional superhydrophobic surfaces have been prepared. An example of a bionic or biomimetic superhydrophobic material in nanotechnology is nanopin film . One study presents a vanadium pentoxide surface that switches reversibly between superhydrophobicity and superhydrophilicity under the influence of UV radiation. According to

624-519: Is caused by a cascade of enzymatic reactions. The first of these reactions takes place when the ubiquitin-activating enzyme E1 hydrolyses ATP and forms a high-energy thioester linkage between a cysteine residue in its active site and the C-terminus of ubiquitin. The resulting activated ubiquitin is then passed to E2, which is a ubiquitin-conjugating enzyme . Another group of enzymes, more specifically ubiquitin protein ligases called E3, bind to

672-509: Is crucial for their export. HIV uses an efficient mechanism to dislocate a single-membrane-spanning host protein, CD4 , from the ER and submits it to ERAD. The Vpu protein of HIV-1 is a protein on the ER membrane and targets newly made CD4 in the endoplasmic reticulum for degradation by cytosolic proteasomes. Vpu only utilizes part of the ERAD process to degrade CD4. CD4 is normally a stable protein and

720-449: Is estimated that 20–30% of all genes in most genomes encode for membrane proteins. For instance, about 1000 of the ~4200 proteins of E. coli are thought to be membrane proteins, 600 of which have been experimentally verified to be membrane resident. In humans, current thinking suggests that fully 30% of the genome encodes membrane proteins. Membrane proteins are the targets of over 50% of all modern medicinal drugs . Among

768-434: Is mostly an entropic effect originating from the disruption of the highly dynamic hydrogen bonds between molecules of liquid water by the nonpolar solute, causing the water to form a clathrate -like structure around the non-polar molecules. This structure formed is more highly ordered than free water molecules due to the water molecules arranging themselves to interact as much as possible with themselves, and thus results in

816-550: Is not likely to be a target for ERAD. However, HIV produces the membrane protein Vpu that binds to CD4. The Vpu protein mainly retains the CD4 in the ER by SCFβ-TrCP-dependent ubiquitination of the CD4 cytosolic tail and transmembrane domain (TMD) interactions. The CD4 Gly415 is a contributor to CD4-Vpu interactions, several TMD-mediated mechanisms by HIV-1 Vpu are necessary to downregulate CD4 and thus promote viral pathogenesis. CD4 retained in

864-475: Is predicated on their cleanliness, has improved the "self-cleaning" of these surfaces. Scalable and sustainable hydrophobic PDRCs that avoid VOCs have further been developed. Membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes . Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are

912-672: Is subsequently degraded by the proteasome. Vpu itself escapes from the degradation. The big open questions related to ERAD are: Hydrophobic In chemistry , hydrophobicity is the chemical property of a molecule that is seemingly repelled from a mass of water (called a hydrophobe ). In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thus, prefer other neutral molecules and nonpolar solvents . Because water molecules are polar, hydrophobes do not dissolve well among them. Hydrophobic molecules in water often cluster together, forming micelles . Water on hydrophobic surfaces will exhibit

960-403: Is termed contact angle hysteresis and can be used to characterize surface heterogeneity, roughness, and mobility. Surfaces that are not homogeneous will have domains that impede motion of the contact line. The slide angle is another dynamic measure of hydrophobicity and is measured by depositing a droplet on a surface and tilting the surface until the droplet begins to slide. In general, liquids in

1008-452: Is termed the advancing contact angle. The receding contact angle is now measured by pumping the liquid back out of the droplet. The droplet will decrease in volume, the contact angle will decrease, but its three-phase boundary will remain stationary until it suddenly recedes inward. The contact angle the droplet had immediately before receding inward is termed the receding contact angle. The difference between advancing and receding contact angles

SECTION 20

#1732772769245

1056-509: Is widely thought that this driving force is provided by ubiquitin-binding factors. One of these ubiquitin-binding factors is the Cdc48p-Npl4p-Ufd1p complex in yeast. Humans have the homolog of Cdc48p known as valosin-containing protein (VCP/p97) with the same function as Cdc48p. VCP/p97 transports substrates from the endoplasmic reticulum to the cytoplasm with its ATPase activity. The ubiquitination of terminally misfolded proteins

1104-478: The lipid bilayer or to integral proteins by a combination of hydrophobic , electrostatic , and other non-covalent interactions. Peripheral proteins dissociate following treatment with a polar reagent, such as a solution with an elevated pH or high salt concentrations. Integral and peripheral proteins may be post-translationally modified, with added fatty acid , diacylglycerol or prenyl chains, or GPI (glycosylphosphatidylinositol), which may be anchored in

1152-414: The 26S proteasome. Hereafter, the polypeptide chain is fed into the central chamber of the 20S core region that contains the proteolytically active sites. Ubiquitin is cleaved before terminal digestion by deubiquitinating enzymes. This third step is very closely associated with the second one, since ubiquitination takes place during the translocation event. However, the proteasomal degradation takes place in

1200-552: The Cassie–Baxter state exhibit lower slide angles and contact angle hysteresis than those in the Wenzel state. Dettre and Johnson discovered in 1964 that the superhydrophobic lotus effect phenomenon was related to rough hydrophobic surfaces, and they developed a theoretical model based on experiments with glass beads coated with paraffin or TFE telomer. The self-cleaning property of superhydrophobic micro- nanostructured surfaces

1248-399: The Cassie–Baxter state is more mobile than in the Wenzel state. We can predict whether the Wenzel or Cassie–Baxter state should exist by calculating the new contact angle with both equations. By a minimization of free energy argument, the relation that predicted the smaller new contact angle is the state most likely to exist. Stated in mathematical terms, for the Cassie–Baxter state to exist,

1296-501: The ER will be a target for a variant ERAD pathway rather than predominantly appearing at the plasma membrane without the presence of Vpu through the RESET pathway. Vpu mediates the CD4 retention in the ER and the addition of degradation. As Vpu is phosphorylated , it mimics substrates for the E3 complex SCF. In cells that are infected with HIV, SCF interacts with Vpu and ubiquitinates CD4, which

1344-416: The applicability of the Wenzel and Cassie–Baxter models. In an experiment designed to challenge the surface energy perspective of the Wenzel and Cassie–Baxter model and promote a contact line perspective, water drops were placed on a smooth hydrophobic spot in a rough hydrophobic field, a rough hydrophobic spot in a smooth hydrophobic field, and a hydrophilic spot in a hydrophobic field. Experiments showed that

1392-543: The cytoplasm. The ER membrane anchored RING finger containing ubiquitin ligases Hrd1 and Doa10 are the major mediators of substrate ubiquitination during ERAD. The tail anchored membrane protein Ubc6 as well as Ubc1 and the Cue1 dependent membrane bound Ubc7 are the ubiquitin conjugating enzymes involved in ERAD. As the variation of ERAD-substrates is enormous, several variations of the ERAD mechanism have been proposed. Indeed, it

1440-402: The electrons reduce V to V . The oxygen vacancies are met by water, and it is this water absorbency by the vanadium surface that makes it hydrophilic. By extended storage in the dark, water is replaced by oxygen and hydrophilicity is once again lost. A significant majority of hydrophobic surfaces have their hydrophobic properties imparted by structural or chemical modification of a surface of

1488-420: The following inequality must be true. A recent alternative criterion for the Cassie–Baxter state asserts that the Cassie–Baxter state exists when the following 2 criteria are met:1) Contact line forces overcome body forces of unsupported droplet weight and 2) The microstructures are tall enough to prevent the liquid that bridges microstructures from touching the base of the microstructures. A new criterion for

Endoplasmic-reticulum-associated protein degradation - Misplaced Pages Continue

1536-499: The glycoprotein and the latter is recognized by EDEM. Eventually EDEM will target the misfolded glycoproteins for degradation by facilitating binding of ERAD lectins OS9 and XTP3-B. Because the ubiquitin–proteasome system (UPS) is located in the cytosol, terminally misfolded proteins have to be transported from the endoplasmic reticulum back into cytoplasm. Most evidence suggest that the Hrd1 E3 ubiquitin-protein ligase can function as

1584-830: The human diseases in which membrane proteins have been implicated are heart disease , Alzheimer's and cystic fibrosis . Although membrane proteins play an important role in all organisms, their purification has historically, and continues to be, a huge challenge for protein scientists. In 2008, 150 unique structures of membrane proteins were available, and by 2019 only 50 human membrane proteins had had their structures elucidated. In contrast, approximately 25% of all proteins are membrane proteins. Their hydrophobic surfaces make structural and especially functional characterization difficult. Detergents can be used to render membrane proteins water-soluble , but these can also alter protein structure and function. Making membrane proteins water-soluble can also be achieved through engineering

1632-416: The latter accumulate and damage the cell. An example of a disease caused by this first group of disorders is Parkinson's disease . It is caused by a mutation in the parkin gene . Parkin is a protein that functions in complex with CHIP as a ubiquitin ligase and overcomes the accumulation and aggregation of misfolded proteins. [There are numerous theories addressing the causes of Parkinson's disease, besides

1680-425: The leaves of the lotus plant, are those that are extremely difficult to wet. The contact angles of a water droplet exceeds 150°. This is referred to as the lotus effect , and is primarily a chemical property related to interfacial tension , rather than a chemical property. In 1805, Thomas Young defined the contact angle θ by analyzing the forces acting on a fluid droplet resting on a solid surface surrounded by

1728-509: The lipid bilayer. Polypeptide toxins and many antibacterial peptides , such as colicins or hemolysins , and certain proteins involved in apoptosis , are sometimes considered a separate category. These proteins are water-soluble but can undergo significant conformational changes , form oligomeric complexes and associate irreversibly or reversibly with the lipid bilayer . Membrane proteins, like soluble globular proteins , fibrous proteins , and disordered proteins , are common. It

1776-415: The localization of hydrophobic amino acid sequences. Integral membrane proteins are permanently attached to the membrane. Such proteins can be separated from the biological membranes only using detergents , nonpolar solvents , or sometimes denaturing agents. They can be classified according to their relationship with the bilayer : Peripheral membrane proteins are temporarily attached either to

1824-458: The mid-20th century. Active recent research on superhydrophobic materials might eventually lead to more industrial applications. A simple routine of coating cotton fabric with silica or titania particles by sol-gel technique has been reported, which protects the fabric from UV light and makes it superhydrophobic. An efficient routine has been reported for making polyethylene superhydrophobic and thus self-cleaning. 99% of dirt on such

1872-410: The misfolded protein. Next they align the protein and E2, thus facilitating the attachment of ubiquitin to lysine residues of the misfolded protein. Following successive addition of ubiquitin molecules to lysine residues of the previously attached ubiquitin, a polyubiquitin chain is formed. A polyubiquitinated protein is produced and this is recognized by specific subunits in the 19S capping complexes of

1920-454: The one presented here. Many of these can be found in the section of Misplaced Pages devoted to causes of Parkinson's disease .] In contrast to this first group of disorders, the second group is caused by premature degradation of secretory or membrane proteins. In this way, these proteins aren't able to be deployed to distal compartments, as is the case in cystic fibrosis . As described before, the addition of polyubiquitin chains to ERAD substrates

1968-521: The opportunity to reach their native conformation. They can do this by way of reglucosylating these glycoproteins by an enzyme called UDP - glucose - glycoprotein glucosyltransferase also known as UGGT . Terminally misfolded proteins, however, must be extracted from CNX/CRT. This is carried out by members of the EDEM (ER degradation-enhancing α-mannosidase-like protein) family (EDEM1-3) and ER mannosidase I. This mannosidase removes one mannose residue from

Endoplasmic-reticulum-associated protein degradation - Misplaced Pages Continue

2016-408: The original. However, a hydrophilic surface (one that has an original contact angle less than 90°) becomes more hydrophilic when microstructured – its new contact angle becomes less than the original. Cassie and Baxter found that if the liquid is suspended on the tops of microstructures, θ will change to θ CB* : where φ is the area fraction of the solid that touches the liquid. Liquid in

2064-421: The study, any surface can be modified to this effect by application of a suspension of rose-like V 2 O 5 particles, for instance with an inkjet printer . Once again hydrophobicity is induced by interlaminar air pockets (separated by 2.1 nm distances). The UV effect is also explained. UV light creates electron-hole pairs , with the holes reacting with lattice oxygen, creating surface oxygen vacancies, while

2112-437: The surface chemistry and geometry at the contact line affected the contact angle and contact angle hysteresis , but the surface area inside the contact line had no effect. An argument that increased jaggedness in the contact line enhances droplet mobility has also been proposed. Many hydrophobic materials found in nature rely on Cassie's law and are biphasic on the submicrometer level with one component air. The lotus effect

2160-509: The switch between Wenzel and Cassie-Baxter states has been developed recently based on surface roughness and surface energy . The criterion focuses on the air-trapping capability under liquid droplets on rough surfaces, which could tell whether Wenzel's model or Cassie-Baxter's model should be used for certain combination of surface roughness and energy. Contact angle is a measure of static hydrophobicity, and contact angle hysteresis and slide angle are dynamic measures. Contact angle hysteresis

2208-494: The two terms are not synonymous. While hydrophobic substances are usually lipophilic, there are exceptions, such as the silicones and fluorocarbons . The term hydrophobe comes from the Ancient Greek ὑδρόφοβος ( hydróphobos ), "having a fear of water", constructed from Ancient Greek ὕδωρ (húdōr)  'water' and Ancient Greek φόβος (phóbos)  'fear'. The hydrophobic interaction

2256-585: Was confirmed that soluble , membrane and transmembrane proteins were recognized by different mechanisms. This led to the identification of 3 different pathways that constitute in fact 3 checkpoints. As ERAD is a central element of the secretory pathway, disorders in its activity can cause a range of human diseases. These disorders can be classified into two groups. The first group is the result of mutations in ERAD components, which subsequently lose their function. By losing their function, these components are no longer able to stabilize aberrant proteins, so that

2304-457: Was reported in 1977. Perfluoroalkyl, perfluoropolyether, and RF plasma -formed superhydrophobic materials were developed, used for electrowetting and commercialized for bio-medical applications between 1986 and 1995. Other technology and applications have emerged since the mid-1990s. A durable superhydrophobic hierarchical composition, applied in one or two steps, was disclosed in 2002 comprising nano-sized particles ≤ 100 nanometers overlaying

#244755