CD59
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CD59
CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the ''CD59'' gene. It is an LU domain and belongs to the LY6/ uPAR/ alpha-neurotoxin protein family. CD59 attaches to host cells via a glycophosphatidylinositol (GPI) anchor. Cholesterol-containing microdomains aid in CD59 activity by stimulating a "pinch point" in the lipid membrane during MAC assembly to prevent pore-formation and inhibit lysing. When complement activation leads to deposition of C5b678 on host cells, CD59 can prevent C9 from polymerizing and forming the complement membrane attack complex. It may also signal the cell to perform active measures such as endocytosis of the CD59-C9 complex. Endocytosis of this complex leads to the destruction of the ion channel formation that this complex provides to the MAC. These ion channels are used for transfer of different ions to maintain the correct conce ...
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Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an ''intravascular'' hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation. Research suggests that PNH thrombosis (a blood clot) is caused by both the absence of GPI-anchored complement regulatory proteins (CD55 and CD59) on PNH platelets and the excessive consumption of nitric oxide (NO). PNH is the only hemolytic anemia caused by an ''acquired'' (rather than inherited) intr ...
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LU Domain
The LU domain ( Ly-6 antigen/ uPAR) is an evolutionarily conserved protein domain of the three-finger protein superfamily. This domain is found in the extracellular domains of cell-surface receptors and in either GPI-anchored or secreted globular proteins, for example the Ly-6 family, CD59, and Sgp-2. A variety of GPI-linked cell-surface glycoproteins are composed of one or more copies of a conserved LU domain of about 100 amino-acid residues. Among these proteins, most contain only a single LU domain, though small numbers of exceptions are known; well-studied family member uPAR has three tandem LU domains. Structure This domain folds into five antiparallel beta sheets, a structure common to the three-finger protein family. The domain typically contains ten well- conserved cysteine residues involved in five disulfide bonds, though some examples such as two of the three uPAR domains have fewer. Examples Besides uPAR, other receptors with LU domains include members of the ...
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Decay-accelerating Factor
Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the ''CD55'' gene. DAF regulates the complement system on the Cell (biology), cell surface. It recognizes C4b and C3b fragments that are created during activation of C4 (classical complement pathway, classical or lectin pathway, lectin pathway) or C3 (alternative complement pathway, alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2a C3-convertase, and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complement cascade, DAF indirectly blocks the formation of the membrane attack complex. This glycoprotein is broadly distributed among he ...
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Complement System
The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. Despite being part of the innate immune system, the complement system can be recruited and brought into action by antibodies generated by the adaptive immune system. The complement system consists of a number of small, inactive, liver synthesized protein precursors circulating in the blood. When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end result of this ''complement activation'' or ''complement fixation'' cascade is stimulation of phagocytes to clear foreign and damaged material, inflammation to attract additional phagocytes, and activation of the cell-killi ...
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Complement Membrane Attack Complex
The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector of the immune system. Antibody-mediated complement activation leads to MAC deposition on the surface of infected cells. Assembly of the MAC leads to pores that disrupt the cell membrane of target cells, leading to cell lysis and death. The MAC is composed of the complement components C5b, C6, C7, C8 and several C9 molecules. A number of proteins participate in the assembly of the MAC. Freshly activated C5b binds to C6 to form a C5b-6 complex, then to C7 forming the C5b-6-7 complex. The C5b-6-7 complex binds to C8, which is composed of three chains (alpha, beta, and gamma), thus forming the C5b-6-7-8 complex. C5b-6-7-8 subsequently binds to C9 and acts as a catalyst in the polymerization of C9. Structure and function MAC is compos ...
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Glycophosphatidylinositol
Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes. GPI is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to the inositol residue) and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane. Synthesis Glycosylated (GPI-anchored) proteins contain a signal sequence, thus directing them to the endoplasmic reticulum (ER). The protein is co-translationally inserted in the ER membrane via a translocon and is attached to the ER membrane by its hydrophobic C terminus; the majority of the protein extends into the ER lumen. The hydro ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ...
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Clusters Of Differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371 (). Nomenclature The CD nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Paris in 1982. This system was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the surface mole ...
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MCF-7
MCF-7 is a breast cancer cell line isolated in 1970 from a 69-year-old woman. MCF-7 is the acronym of Michigan Cancer Foundation-7, referring to the institute in Detroit where the cell line was established in 1973 by Herbert Soule and co-workers. The Michigan Cancer Foundation is now known as the Barbara Ann Karmanos Cancer Institute. Prior to MCF-7, it was not possible for cancer researchers to obtain a mammary cell line that was capable of living longer than a few months. The patient, Frances Mallon died in 1970 due to metastatic breast cancer. Her cells were the source of much of current knowledge about breast cancer. At the time of sampling, she was a nun in the convent of Sisters, Servants of the Immaculate Heart of Mary, Immaculate Heart of Mary in Monroe, Michigan under the name of Sister Catherine Frances. MCF-7 and two other breast cancer cell lines, named T-47D and MDA-MB-231, account for more than two-thirds of all abstracts reporting studies on mentioned breast canc ...
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Viral Envelope
A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. A viral envelope protein or E protein is a protein in the envelope, which may be acquired by the capsid from an infected host cell. Host cell infection process Numerous human pathogenic viruses in circulation are encased in lipid bilayers, and they infect their target cells by causing the viral envelope and cell membrane to fuse. Although there are effective vaccines against some of these viruses, there is no preventative or curative medicine for the majority of them. In most cases, the known vaccines operate by inducing antibodies that prevent the pathogen from entering cells. This happens in the case of enveloped viruses when the antibodies bind to the viral envelope proteins. The membrane fusion event that triggers viral entrance is caused by the viral membrane fusion protein. Many envelo ...
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Vaccinia Virus
The vaccinia virus (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250  nm, with a mass of approximately 5–10 fg. The vaccinia virus is the source of the modern smallpox vaccine, which the World Health Organization (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although ''smallpox'' no longer exists in the wild, ''vaccinia'' virus is still studied widely by scientists as a tool for gene therapy and genetic engineering. Smallpox had been an endemic human disease that had a 30% fatality rate. In 1796, the British doctor Edward Jenner proved that an infection with the relatively mild cowpox virus would also confer immunity to the deadly smallpox. Jenner referred to cowpox as ''variolae vaccinae'' (smallpox of the cow). However, the ...
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Cytomegalovirus
''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherpesvirinae''. Humans and other primates serve as natural hosts. The 11 species in this genus include '' human betaherpesvirus 5'' (HCMV, human cytomegalovirus, HHV-5), which is the species that infects humans. Diseases associated with HHV-5 include mononucleosis and pneumonia, and congenital CMV in infants can lead to deafness and ambulatory problems. In the medical literature, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses. MX2/MXB protein was identified as a restriction factor for herpesviruses, which acts at a very early stage of the replication cycle and MX2/MXB restriction of herpesvirus requires GTPase activity. Taxonomy Within the '' Her ...
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