キメラタンパク質、キメラタンパク、キメラ蛋白、キメラ蛋白質

WordNet

any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
being or relating to or like a chimera; "his Utopia is not as chimeric commonwealth but a practical improvement on what already exists"- Douglas Bush (同)chimerical, chimeral

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蛋白(たんばく)質
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/17 11:24:08」(JST)

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Fusion proteins or chimeric proteins (literally, made of parts from different sources) are proteins created through 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 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 is considered to be the primary oncogenic driver of chronic myelogenous leukemia.

Functions

Some fusion proteins combine whole peptides and therefore contains all functional domains of the original proteins. However, other fusion proteins, especially those that are naturally occurring, 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 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 potential to result in new proteins with novel functions.

Recombinant technology

A recombinant fusion protein is a protein created through genetic engineering of 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 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 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.

Chimeric protein drugs

Sketches of mouse (top-left), chimeric (top-right) and humanized (bottom-left) monoclonal antibodies. Human parts are shown in brown, and non-human parts in blue.

The purpose of creating fusion proteins in drug development 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 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 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, is a TNFα blocker created through the combination of a tumor necrosis factor receptor (TNFR) with the immunoglobulin G1 Fc segment. TNFR provides specificity for the drug target and the antibody Fc segment is believed to add stability and deliverability of the drug.

Natural occurrence

Naturally occurring fusion genes are most commonly created when 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:

Gag-onc fusion protein
Bcr-abl fusion protein
Tpr-met fusion protein

Antibodies are fusion proteins produced by VDJ recombination.

External links

Mutant Chimeric Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)

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English Journal

Novel treatment of acute promyelocytic leukemia: As₂O₃, retinoic acid and retinoid pharmacology.

Zhu G, Mische SE, Seigneres B1.
Current pharmaceutical biotechnology.Curr Pharm Biotechnol.2014 Oct;14(9):849-58.
Acute promyelocytic leukemia(APL), a specific characteristic of t(15;17) chromosome translocation, represents 5% to 15% of cases of acute nonlymphocytic leukemia. An alternative approach is to consider retinoic acid(all-trans RA, ATRA or 13-cis RA or 9-cis RA) plus chemotherapy or RA plus As₂O₃
PMID 24433507

A recombinant humanized anti-cocaine monoclonal antibody inhibits the distribution of cocaine to the brain in rats.

Norman AB1, Gooden FC2, Tabet MR2, Ball WJ2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2014 Jul;42(7):1125-31. doi: 10.1124/dmd.114.057034. Epub 2014 Apr 14.
The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd) and specificity for cocaine over its inactive metabolites benz
PMID 24733787

The effect of acidic pH on the inhibitory efficacy of peptides against the interaction ICAM-1/LFA-1 studied by surface plasmon resonance (SPR).

Wu SH1, Núnez D2, Hu SY3, Domingo MP4, Chen YC5, Wei PK1, Pardo J6, Gálvez EM7, Chiou A8.
Biosensors & bioelectronics.Biosens Bioelectron.2014 Jun 15;56:159-66. doi: 10.1016/j.bios.2014.01.008. Epub 2014 Jan 16.
Synthetic peptides have been developed for therapeutic applications for decades. The therapeutic efficacy often depends not only on the stabilization of the peptides but also on their binding specificity and affinity to the target molecules to interfere with designated molecular interaction. In this
PMID 24487103

Japanese Journal

Improved protective efficacy of a chimeric Staphylococcus aureus vaccine candidate iron-regulated surface determinant B (N126–P361)-target of RNAⅢ activating protein in mice

Yu Liquan,Wang Ning,Ma Jinzhu [他]
Microbiology and immunology 57(12), 857-864, 2013-12
NAID 40019940720

Immunogenicity of EIT chimeric protein expressed in transplastomic tobacco plants towards development of an oral vaccine against Escherichia coli O157:H7

Karimi Farrokh,Mousavi Amir,Salmanian Ali Hatef [他]
Plant biotechnology reports 7(4), 535-546, 2013-10
NAID 40019926685

Involvement of TRPM2 in Peripheral Nerve Injury-Induced Infiltration of Peripheral Immune Cells into the Spinal Cord in Mouse Neuropathic Pain Model.

Isami Kouichi,Haraguchi Kayo,So Kanako,Asakura Kayoko,Shirakawa Hisashi,Mori Yasuo,Nakagawa Takayuki,Kaneko Shuji
PloS one 8(7), 2013-07-30
… To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages) into the injured nerve and spinal cord by using bone marrow (BM) chimeric mice by crossing wildtype (WT) and TRPM2-knockout (TRPM2-KO) mice. …
NAID 120005312062

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リンク元	「キメラ蛋白質」「キメラ蛋白」「キメラタンパク」「キメラタンパク質」
拡張検索	「mutant chimeric protein」
関連記事	「chimeric」