4QKX , 2R4R , 2R4S , 2RH1 , 3D4S , 3KJ6 , 3NY8 , 3NY9 , 3NYA , 3P0G , 3PDS , 3SN6 , 4GBR , 4LDE , 4LDL , 4LDO , 5D5A , 5D5B , 5JQH
31-404: (Redirected from Beta-2 ) Beta 2 ( β2 ), may stand for: Beta-2 adrenergic receptor Beta 2 Limited NeuroD1 , transcription factor TGF beta 2 Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title Beta 2 . If an internal link led you here, you may wish to change
62-489: A chromosomal translocation replaces the terminal exons of one gene with intact exons from a second gene. This creates a single gene that can be transcribed , spliced , and translated to produce a functional fusion protein. Many important cancer -promoting oncogenes are fusion genes produced in this way. Examples include: Antibodies are fusion proteins produced by V(D)J recombination . There are also rare examples of naturally occurring polypeptides that appear to be
93-569: A beta-agonist, but rather an anabolic agent. These effects are largely attractive within agricultural contexts insofar that β 2 adrenergic agents have seen notable extra-label usage in food-producing animals and livestock. While many countries including the United States have prohibited extra-label usage in food-producing livestock, the practice is still observed in many countries. In the normal eye, beta-2 stimulation by salbutamol increases intraocular pressure via net: In glaucoma , drainage
124-405: A complex mutation , such as a chromosomal translocation , tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoproteins . The bcr-abl fusion protein is a well-known example of an oncogenic fusion protein, and
155-401: A fusion gene. This typically involves removing the stop codon from a cDNA sequence coding for the first protein, then appending the cDNA sequence of the second protein in frame through ligation or overlap extension PCR . That DNA sequence will then be expressed by a cell as a single protein. The protein can be engineered to include the full sequence of both original proteins, or only
186-444: A host cell is a widely popular technique used in experimental cell and biology research in order to track protein interactions in real time. The first fluorescent tag, green fluorescent protein (GFP), was isolated from Aequorea victoria and is still used frequently in modern research. More recent derivations include photoconvertible fluorescent proteins (PCFPs), which were first isolated from Anthozoa . The most commonly used PCFP
217-603: A model system which earned them the 2012 Nobel Prize in Chemistry “for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein-coupled-receptors”. The official symbol for the human gene encoding the β 2 adrenoreceptor is ADRB2 . The ADRB2 gene is intronless . Different polymorphic forms, point mutations , and/or downregulation of this gene are associated with nocturnal asthma , obesity and type 2 diabetes . The 3D crystallographic structure (see figure and links to
248-414: A portion of either. If the two entities are proteins, often linker (or "spacer") peptides are also added, which make it more likely that the proteins fold independently and behave as expected. Especially in the case where the linkers enable protein purification , linkers in protein or peptide fusions are sometimes engineered with cleavage sites for proteases or chemical agents that enable the liberation of
279-436: Is a TNFα blocker created through the combination of a tumor necrosis factor receptor (TNFR) with the immunoglobulin G 1 Fc segment . TNFR provides specificity for the drug target and the antibody Fc segment is believed to add stability and deliverability of the drug. Additional chimeric proteins used for therapeutic applications include: A recombinant fusion protein is a protein created through genetic engineering of
310-462: Is a cell membrane-spanning beta-adrenergic receptor that binds epinephrine (adrenaline), a hormone and neurotransmitter whose signaling, via adenylate cyclase stimulation through trimeric G s proteins , increases cAMP , and, via downstream L-type calcium channel interaction, mediates physiologic responses such as smooth muscle relaxation and bronchodilation. Robert J. Lefkowitz and Brian Kobilka studied beta 2 adrenergic receptor as
341-485: Is considered to be the primary oncogenic driver of chronic myelogenous leukemia . Some fusion proteins combine whole peptides and therefore contain all functional domains of the original proteins. However, other fusion proteins, especially those that occur naturally, combine only portions of coding sequences and therefore do not maintain the original functions of the parental genes that formed them. Many whole gene fusions are fully functional and can still act to replace
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#1732927241221372-613: Is reduced (open-angle glaucoma) or blocked completely (closed-angle glaucoma). In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol may be employed. ( Beta blockers ) * denotes selective antagonist to the receptor. Beta-2 adrenergic receptor has been shown to interact with: Fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through
403-494: Is the Kaede fluorescent tag, but the development of Kikume green-red (KikGR) in 2005 offers a brighter signal and more efficient photoconversion. The advantage of using PCFP fluorescent tags is the ability to track the interaction of overlapping biochemical pathways in real time. The tag will change color from green to red once the protein reaches a point of interest in the pathway, and the alternate colored protein can be monitored through
434-487: Is to impart properties from each of the "parent" proteins to the resulting chimeric protein. Several chimeric protein drugs are currently available for medical use. Many chimeric protein drugs are monoclonal antibodies whose specificity for a target molecule was developed using mice and hence were initially "mouse" antibodies. As non-human proteins, mouse antibodies tend to evoke an immune reaction if administered to humans. The chimerization process involves engineering
465-412: The duration of pathway. This technique is especially useful when studying G-protein coupled receptor (GPCR) recycling pathways. The fates of recycled G-protein receptors may either be sent to the plasma membrane to be recycled, marked by a green fluorescent tag, or may be sent to a lysosome for degradation, marked by a red fluorescent tag. The purpose of creating fusion proteins in drug development
496-579: The following properties: The earliest applications of recombinant protein design can be documented in the use of single peptide tags for purification of proteins in affinity chromatography . Since then, a variety of fusion protein design techniques have been developed for applications as diverse as fluorescent protein tags to recombinant fusion protein drugs. Three commonly used design techniques include tandem fusion, domain insertion, and post-translational conjugation. The proteins of interest are simply connected end-to-end via fusion of N or C termini between
527-519: The formation of cyclic adenosine monophosphate (cAMP) which then activates protein kinase A , and counterbalancing phosphatase PP2A . Protein kinase A then goes on to phosphorylate (and thus inactivate) myosin light-chain kinase , which causes smooth muscle relaxation, accounting for the vasodilatory effects of beta 2 stimulation. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling. A two-state biophysical and molecular model has been proposed to account for
558-406: The functionality of the protein domains of interest. This technique involves the fusion of consecutive protein domains by encoding desired structures into a single polypeptide chain, but sometimes may require insertion of a domain within another domain. This technique is typically regarding as more difficult to carry out than tandem fusion, due to difficulty finding an appropriate ligation site in
589-765: The gene of interest. This technique fuses protein domains following ribosomal translation of the proteins of interest, in contrast to genetic fusion prior to translation used in other recombinant technologies. Protein linkers aid fusion protein design by providing appropriate spacing between domains, supporting correct protein folding in the case that N or C termini interactions are crucial to folding. Commonly, protein linkers permit important domain interactions, reinforce stability, and reduce steric hindrance, making them preferred for use in fusion protein design even when N and C termini can be fused. Three major types of linkers are flexible, rigid, and in vivo cleavable. Naturally occurring fusion genes are most commonly created when
620-558: The joining of two or more genes that originally coded for separate proteins. Translation of this fusion gene results in a single or multiple polypeptides with functional properties derived from each of the original proteins. Recombinant fusion proteins are created artificially by recombinant DNA technology for use in biological research or therapeutics . Chimeric or chimera usually designate hybrid proteins made of polypeptides having different functions or physico-chemical patterns. Chimeric mutant proteins occur naturally when
651-603: The link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=Beta_2&oldid=1099038823 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Beta-2 adrenergic receptor 154 11555 ENSG00000169252 ENSMUSG00000045730 P07550 P18762 NM_000024 NM_007420 NP_000015 NP_031446 The beta-2 adrenergic receptor (β 2 adrenoreceptor), also known as ADRB2 ,
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#1732927241221682-439: The original peptides. Some, however, experience interactions between the two proteins that can modify their functions. Beyond these effects, some gene fusions may cause regulatory changes that alter when and where these genes act. For partial gene fusions , the shuffling of different active sites and binding domains have the potential to result in new proteins with novel functions. The fusion of fluorescent tags to proteins in
713-430: The pH and REDOX sensitivity of this and other GPCRs. Beta-2 adrenergic receptors have also been found to couple with G i , possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 adrenergic receptors are coupled only to G s , and stimulation of these results in a more diffuse cellular response. This appears to be mediated by cAMP induced PKA phosphorylation of
744-406: The proteins. This provides a flexible bridge structure allowing enough space between fusion partners to ensure proper folding . However, the N or C termini of the peptide are often crucial components in obtaining the desired folding pattern for the recombinant protein, making simple end-to-end conjoining of domains ineffective in this case. For this reason, a protein linker is often needed to maintain
775-905: The receptor. Interestingly, Beta-2 adrenergic receptor was observed to localize exclusively to the T-tubular network of adult cardiomyocytes, as opposed to Beta-1 adrenergic receptor, which is observed also on the outer plasma membrane of the cell Activation of the β 2 adrenoreceptor with long-acting agents such as oral clenbuterol and intravenously-infused albuterol results in skeletomuscular hypertrophy and anabolism. The comprehensive anabolic, lipolytic, and ergogenic effects of long-acting β 2 agonists such as clenbuterol render them frequent targets as performance-enhancing drugs in athletes. Consequently, such agents are monitored for and generally banned by WADA (World Anti-Doping Agency) with limited permissible usage under therapeutic exemptions; clenbuterol and other β 2 adrenergic agents remain banned not as
806-450: The replacement of segments of the antibody molecule that distinguish it from a human antibody. For example, human constant domains can be introduced, thereby eliminating most of the potentially immunogenic portions of the drug without altering its specificity for the intended therapeutic target. Antibody nomenclature indicates this type of modification by inserting -xi- into the non-proprietary name (e.g., abci- xi -mab ). If parts of
837-444: The right) of the β 2 -adrenergic receptor has been determined by making a fusion protein with lysozyme to increase the hydrophilic surface area of the protein for crystal contacts. An alternative method, involving production of a fusion protein with an agonist, supported lipid-bilayer co-crystallization and generation of a 3.5 Å resolution structure. The crystal structure of the β 2 Adrenergic Receptor-G s protein complex
868-665: The two separate proteins. This technique is often used for identification and purification of proteins, by fusing a GST protein , FLAG peptide , or a hexa-his peptide (6xHis-tag), which can be isolated using affinity chromatography with nickel or cobalt resins. Di- or multimeric chimeric proteins can be manufactured through genetic engineering by fusion to the original proteins of peptide domains that induce artificial protein di- or multimerization (e.g., streptavidin or leucine zippers ). Fusion proteins can also be manufactured with toxins or antibodies attached to them in order to study disease development. Hydrogenase promoter, P SH ,
899-430: The variable domains are also replaced by human portions, humanized antibodies are obtained. Although not conceptually distinct from chimeras, this type is indicated using -zu- such as in dacli- zu -mab . See the list of monoclonal antibodies for more examples. In addition to chimeric and humanized antibodies, there are other pharmaceutical purposes for the creation of chimeric constructs. Etanercept , for example,
930-461: Was solved in 2011. The largest conformational changes in the β2AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an alpha helical extension of the cytoplasmic end of TM5. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca V 1.2. This receptor-channel complex is coupled to the G s G protein , which activates adenylyl cyclase , catalysing
961-475: Was studied constructing a P SH promoter- gfp fusion by using green fluorescent protein ( gfp) reporter gene . Novel recombinant technologies have made it possible to improve fusion protein design for use in fields as diverse as biodetection, paper and food industries, and biopharmaceuticals. Recent improvements have involved the fusion of single peptides or protein fragments to regions of existing proteins, such as N and C termini , and are known to increase