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.
FOP occurs randomly and is not inherited. Experts believe that one cause of fibrodysplasia ossificans progressiva is born with mutations in the ACVR gene what provides the body with instructio...
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 body normally metabolizes substances such as simple sugars and proteins to produce energy, build tissues and many more functions. In the molecular level, chemical reactions such as glycosylation occur, in which a carbohydrate molecule attaches to another protein molecule to form another substance. These chemical reactions are often catalyzed by enzymes resulting in the formation of various glycans, which are involved in many structural and ...
Yan, R., 2011-2012. Reticulon 3 aggregation and its role in the formation of dystrophic neurites. [Online]
CP consists of a single domain with high α-helical content [4]. The N-terminal part this domain is surface exposed whereas the C-terminal region buried in the virion. Several experiments indicate the CP is an O-glycoprotein. Equal amounts of galactose and fructose residues are O-linked to an acetylated serine residue at the N-terminal region [2]. This mediates the formation of a structured...
Schulman, Joshua M., and David E. Fisher. "Abstract." National Center for Biotechnology Information. U.S. National Library of Medicine, 28 Aug. 0005. Web. 24 Apr. 2014.
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.
By utilizing the model yeast S. cerevisiae, Ohsumi found a method for identifying the ATG genes. Ohsumi blocked vacuolar degradation using the yeast mutants, then induced autophagy by starving the cells. With the vacuole impaired, the autophagosomes accumulated in the cell, allowing researchers to simply visualize these compartments, which are generally quite difficult to identify. Ultimately, this technique allowed for the discovery of autophagy genes and mechanisms. (4) This concluded the discovery of the first genes necessary for autophagy. The results displayed that autophagy is controlled by a number of proteins and protein complexes which promote a specific stage of the formation of autophagosomes.
“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 ...
7. Blanchette, Sokol et. al. Type C Niemann- Pick disease. (1988) J. Biol. Chem. :263, 3411-3415.
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). ...
Morris, Colleen A., MD. “Williams Syndrome.” National Center for Biotechnology Information. National Center for Biotechnology Information, 9 Apr. 1999. Web. 13 Feb. 2014. .
Ghosh MK, Borca MV, Roy P. Virus-derived tubular structure displaying foreign sequences on the surface elicit CD4+ Th cell and protective humoral responses. Virology 2002; 302: 383-92.
N-Glycans in eukaryotic cells have a common Man3GlcNAc2 core linked to the Asparagine (Asn) residue in the Asn-X-Ser/Thr sequons of proteins (where X is an amino acid other than proline) and can be classified to high-mannose, complex, and hybrid three types (Figure 1.1). They are presented on many secreted and membrane-bound glycoproteins.