組換え融合タンパク質

WordNet

a nuclear reaction in which nuclei combine to form more massive nuclei with the simultaneous release of energy (同)nuclear_fusion, nuclear fusion reaction
the merging of adjacent sounds or syllables or words
correction of an unstable part of the spine by joining two or more vertebrae; usually done surgically but sometimes done by traction or immobilization (同)spinal_fusion
the act of fusing (or melting) together
an occurrence that involves the production of a union (同)merger, unification
the combining of images from the two eyes to form a single visual percept (同)optical fusion
of or relating to recombinant DNA
a cell or organism in which genetic recombination has occurred
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"

PrepTutorEJDIC

〈U〉(金属などが)溶けること,融解,融合《+『of』+『名』》 / 〈C〉融合物 / 〈C〉(政党・党派などの)連合,合同;(民族などの)融合《+『of』+『名』》 / 〈U〉〈C〉核融合(nuclear fusion)
遺伝子の新結合による
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）』「2014/03/24 12:10:44」(JST)

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This article is about chimeric fusion proteins. For proteins involved in membrane fusion, see membrane fusion protein.

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[edit]

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[edit]

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[edit]

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[edit]

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[edit]

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

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English Journal

Regulation of NKG2D-ligand cell surface expression by intracellular calcium after HDAC-inhibitor treatment.

Jensen H, Hagemann-Jensen M, Lauridsen F, Skov S.SourceLaboratory of Immunology, Section of Biomedicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address: hellejensen@fastmail.fm.
Molecular immunology.Mol Immunol.2013 Mar;53(3):255-64. doi: 10.1016/j.molimm.2012.08.011. Epub 2012 Sep 8.
In this study we demonstrate that histone deacetylase (HDAC)-inhibitor mediated cell surface expression of the structural different NKG2D-ligands MICA/B and ULBP2 is calcium-dependent. Treatment with the calcium chelator EGTA inhibited constitutive as well as HDAC-inhibitor induced MICA/B and ULBP2
PMID 22964480

Preparation of phytoplasma membrane recombinant proteins.

Galetto L, Siampour M, Marzachì C.SourceIstituto di Virologia Vegetale, CNR, Torino, Italy.
Methods in molecular biology (Clifton, N.J.).Methods Mol Biol.2013;938:351-69. doi: 10.1007/978-1-62703-089-2_30.
The study of phytoplasma membrane protein interactions with host cell proteins is crucial to understand the life cycle of these unculturable microorganisms within their hosts. A step-by-step protocol for the heterologous expression of phytoplasma membrane proteins in Escherichia coli is described, t
PMID 22987430

Japanese Journal

A-5 SDF-1担持スキャホールドを用いた骨組織再生誘導(細胞2,一般講演(口頭発表),第65回日本歯科理工学会学術講演会)

伊達智美,中野綾菜,山門奈央,服部栞,平田伊佐雄,谷本幸太郎,加藤功一
日本歯科理工学会誌 34(2), 61, 2015-03-25
… In order to promote bone regeneration using biodegradable polymer scaffolds, attempts were made to prepare recombinant SDF-1 fused with a decapeptide (KLKLKLKLKL; … Since our previous study showed that KL5 had an affinity for biodegradable aliphatic polyesters, the fusion protein (SDF1-KL5) is expected to be stably loaded in a scaffold made of such polyesters, and hence promote recuruitment of bone-forming cells such as endogenous MSCs and OBs into the acaffold. …
NAID 110009923853

Expression and characterization of an M cell-specific ligand-fused dengue virus tetravalent epitope using Saccharomyces cerevisiae (GENETICS, MOLECULAR BIOLOGY, AND GENE ENGINEERING)

Nguyen Ngoc-Luong,So Kum-Kang,Kim Jung-Mi [他],Kim Sae-Hae,Jang Yong-Suk,Yang Moon-Sik,Kim Dae-Hyuk
Journal of bioscience and bioengineering 119(1), 19-27, 2015-01
… A fusion construct (Tet-EDIII-Co1) consisting of an M cell-specific peptide ligand (Co1) at the C-terminus of a recombinant tetravalent gene encoding the amino acid sequences of dengue envelope domain III (Tet-EDIII) from four serotypes was expressed and tested for binding activity to the mucosal immune inductive site M cells for the development of an oral vaccine. …
NAID 110009892228

High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity

Sun Xincheng,Wang Yunlong,Dong Caiwen,Hu Jinqiang,Yang Liping
BioScience Trends 9(4), 221-227, 2015
… The extra domain of influenza M2 protein (M2e) is almost completely conserved among all influenza A virus subtypes. … M2e is a promising candidate target for the development of a broad-spectrum recombinant influenza A vaccine. … Copy numbers of M2e and its fusion expression with different carrier proteins may affect its immunopotency. …
NAID 130005098735