Post-translational modifications have a profound influence on the structure and function of many proteins. Dystroglycan (DG) is an example of a membrane protein that requires extensive post-translational processing in order to function as an extracellular matrix receptor. It is comprised of two subunits, an extracellular -DG subunit and a transmembrane -DG subunit, which are derived by cleavage of a polypeptide encoded by DAG1 (1). The apparent molecular mass (Mr) of -DG as assessed by SDS-PAGE varies from 120- to 200-kDa, due to developmental and tissue-specific post-translational modification of an ~40-kDa core polypeptide (1, 2). Notably, in both muscle and brain, -DG serves as a receptor for extracellular matrix ligands that contain a laminin-G domain—including laminin (1), agrin (3), perlecan (4), and neurexins (5)—and this interaction depends on an unidentified post-translational modification on -DG. -DG is also known as the cellular receptor for lymphocytic choriomeningitis virus (LCMV), Lassa fever virus (LFV), and clade C New World arenaviruses (6, 7). Although the binding sites for LCMV and LFV on -DG have not yet been identified, they are thought to overlap with the modification that is recognized by laminin (8, 9). Mutations in six known or putative glycosyltransferase genes—POMT1 (10), POMT2 (11), POMGnT1 (12), fukutin (13), FKRP (14), and LARGE (15) —have been identified in patients with congenital muscular dystrophies (CMD) classified as “secondary -dystroglycanopathy”. These disorders cover a spectrum of abnormalities affecting the brain, eye, and skeletal muscle, and show a dramatic gradient of phenotypic severity that ranges from the most devastating in Walker-Warburg syndrome (WWS; OMIM# 236670), to...
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...e in vertebrates. Glycoproteins in the cell wall of yeasts and fungi are known to bear phosphodiester-linked glycans that are generated by a process involving phosphorylation on the C6 position of mannose (28). It is interesting that -DG, which is well conserved as an epithelial cell-surface protein from mammals to lower vertebrates, is likewise modified by this ancient type of cell surface glycosylation. A recent study has shown that the most severe form of CMD—WWS—is a genetically heterogeneous disease. Moreover, only 40% of WWS cases are explained by mutations in known CMD-causative genes (POMT1, POMT2, POMGNT1, FCMD, FKRP and LARGE) (28). It is quite likely that a defect in the phosphorylation of O-linked mannose results in severe CMD, and thus our findings provide a new target to be used for the discovery of mutations in novel genes responsible for WWS.
Tay-Sachs disease is a form of these lysosomal storage diseases. It is scientifically known as GM2 gangliosidosis: Hexosaminidase alpha-subunit deficiency. Three polypeptides encoded by three separate locations on the chromosome are needed for the catabolism of GM2 gangliosides. When these genes are mutated, the result is a buildup of the glycosphingolipid GM2 gangliosides. Over 50 mutations have been identified. Tay-Sachs disease is the most common form of gangliosidosis and results from a mutation of the alpha-subunit location on chromosome 15. This causes a severe dysfunction in the enzyme hexosaminidase A.
MCAD normally metabolizes medium-chain acyl-CoAs in the matrix of the mitochondria. In fatty acid β-oxidation, MCAD catalyzes the dehydrogenation of acyl-CoAs with four to 12 carbons in chain length (Matern & Rinaldo, 2012). In MCAD deficiency, this initial dehydrogenation step of the beta-oxidation process if significantly hindered, resulting in ineffective fatty acid degradation. A deficiency in the MCAD enzyme is caused by premature degradation due to an accumulation of improperly folded proteins and tetramer assembly. Beta-oxidation is severely impacted because the enzyme also has reduced enzymatic function due to higher Km values for medium-chain fatty acid substrates and lower affinity for its substrates (Kieweg et al., 1997).
Studies have shown that the antigens responsible for this autoimmune attack have components of the actual desmosome. Two transmembrane glycoproteins have been identified. One being desmoglein ( Dsg) and desmocollin (Dsc). Both of these have three isofor...
Scriver, Charles R, Beaudet, Arthur L, Sly, William S, et al. (2001). The metabolic and molecular bases of inherited disease. 8th ed. London: McGraw-Hill. Pp 1634-1639.
Rabies virus belongs to Lyssavirus genus, Rhadboviridae family. It is a negative-sense, non-segmented, single-strand RNA and 180 nm long* 75 nm wide bullet-shape virus. All rhabdoviruses have two main structural components: a helical ribonucleoprotein (RNP) complex and a surrounding viral envelope. The rabies virus genome encodes five functional proteins: L (transcriptase), N (nucleoprotein), and NS (transcriptase-associated) protein with viral RNA are composed of the RNP complex. This complex adds up in the cytoplasm of neurons that are infected by rabies virus and makes up Negri body that is an indicator of rabies for histopathologists. Another two proteins are M (matrix) and G (glycoprotein) proteins that are associated with the lipid envelope. The G protein shapes the protrusions that are spikes-shape surface antigen on the virion envelope and induce virus-neutralizing antibody.
The Human Cytosolic β-glucosidase is a GH1 enzyme and is present in the liver, kidney, intestine and spleen. It have the same (β/α)8-barrel fold characteristic of GH1 β-glucosidades, and the mainly structural differences between the hCBG and the other GH1 enzymes is confined mainly to loop regions. It does not cont...
β- glucosidases or cellobiases (β- D glucoside glucohydrolases, EC 3.2.1.21)are very important components of the cellulase system in that they complete the hydrolysis to glucose of short-chain oligosaccharides and cellobiose which are released by the ot...
The virus is primarily spherical shaped and roughly 200nm in size, surrounded by a host-cell derived membrane. Its genome is minus-sense single-stranded RNA 16-18 kb in length. It contains matrix protein inside the envelope, hemagglutinin and neuraminidase, fusion protein, nucleocapsid protein, and L and P proteins to form the RNA polymerase. The host-cell receptors on the outside are hemagglutinin and neuraminidase. The virus is allowed to enter the cell when the hemagglutinin/ neuraminidase glycoproteins fuse with the sialic acid on the surface of the host cell, and the capsid enters the cytoplasm. The infected cells express the fusion protein from the virus, and this links the host cells together to create syncitia.
LMNA codes for Lamin A and C, the A type Lamins are the important structural components of the nuclear envelope. The most frequent Hutchinson-Gilford Progeria Syndrome mutation is found at codon 608 (G608G). ...
What is Pompe Disease? Pompe disease is a genetic disorder which deals with a mutation within a gene called the GAA gene, glucosidase, alpha; acid, and produces an enzyme to produce a buildup of glycogen, a complex sugar, within body cells which cause the lysosomes to not reuse the sugar properly. The name of this enzyme is called alpha-glucosidase, more commonly known as acid maltase. The GAA gene is located on Chromosome 17 on the q arm between the positions 25.2 and 25.3 (GAA, paragraph 4). A GAA gene is used to make normal acid maltase which breaks down the glycogen into glucose, a simple sugar molecule. Lysosomes are used to digest, or break down, proteins and sugars for energy. There are different mutations of this gene which causes the disease of Pompe in people. (GAA, paragraph 3) Some of these mutations consist of the alteration of the protein building block, the destruction or inserting of the genetic information located within the GAA gene.
Poliovirus binds to a specific cell surface protein, polio virus receptor (PVR). This protein is an immunoglobin which contains three loops, Ig domains. Polio binds...
“This knowledge will help us design drugs that mimic the viral effects on these proteins to either activate a host’s immune response or shut it down,” said Dr. Michael Gale, associate ...
Sherin, Jonathan E., and Charles B. Nemeroff. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 02 Mar. 0006. Web. 11 Dec. 2013.
...apter 362. Glycogen Storage Diseases and Other Inherited Disorders of Carbohydrate Metabolism. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved January 21, 2012 from http://www.accessmedicine.com/content.aspx?aID=9144477.
The DENV envelope protein E, which is found on the virus surface, has a role as a mediating factor in the initial attachment of the virus to the host cell. Further, several cellular proteins and carbohydrate molecules that act as attachment factors interacting with the viral envelope protein E have been identified. These factors allow the virus population to concentrate on the cell surface thus increasing their chance of access to their target cellular receptor(s). Some of these known molecules that interact with the vi...