4wiq
From Proteopedia
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| - | ''' | + | ==The structure of Murine alpha-Dystroglycan T190M mutant N-terminal domain.== |
| + | <StructureSection load='4wiq' size='340' side='right' caption='[[4wiq]], [[Resolution|resolution]] 1.59Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4wiq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WIQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WIQ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u2c|1u2c]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4wiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wiq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4wiq RCSB], [http://www.ebi.ac.uk/pdbsum/4wiq PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/DAG1_MOUSE DAG1_MOUSE]] The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sacrolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.<ref>PMID:9175728</ref> <ref>PMID:12843252</ref> <ref>PMID:12797959</ref> Alpha-dystroglycan is an extracellular peripheral glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin-G domains, and for certain adenoviruses. Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells. Also receptor for lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses.<ref>PMID:9175728</ref> <ref>PMID:12843252</ref> <ref>PMID:12797959</ref> Beta-dystroglycan is a transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity (By similarity).<ref>PMID:9175728</ref> <ref>PMID:12843252</ref> <ref>PMID:12797959</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The severe dystroglycanopathy known as a form of limb-girdle muscular dystrophy (LGMD2P) is an autosomal recessive disease caused by the point mutation T192M in alpha-dystroglycan. Functional expression analysis in vitro and in vivo indicated that the mutation was responsible for a decrease in posttranslational glycosylation of dystroglycan, eventually interfering with its extracellular-matrix receptor function and laminin binding in skeletal muscle and brain. The X-ray crystal structure of the missense variant T190M of the murine N-terminal domain of alpha-dystroglycan (50-313) has been determined, and showed an overall topology (Ig-like domain followed by a basket-shaped domain reminiscent of the small subunit ribosomal protein S6) very similar to that of the wild-type structure. The crystallographic analysis revealed a change of the conformation assumed by the highly flexible loop encompassing residues 159-180. Moreover, a solvent shell reorganization around Met190 affects the interaction between the B1-B5 anti-parallel strands forming part of the floor of the basket-shaped domain, with likely repercussions on the folding stability of the protein domain(s) and on the overall molecular flexibility. Chemical denaturation and limited proteolysis experiments point to a decreased stability of the T190M variant with respect to its wild-type counterpart. This mutation may render the entire L-shaped protein architecture less flexible. The overall reduced flexibility and stability may affect the functional properties of alpha-dystroglycan via negatively influencing its binding behavior to factors needed for dystroglycan maturation, and may lay the molecular basis of the T190M-driven primary dystroglycanopathy. | ||
| - | The | + | The Structure of the T190M Mutant of Murine alpha-Dystroglycan at High Resolution: Insight into the Molecular Basis of a Primary Dystroglycanopathy.,Bozzi M, Cassetta A, Covaceuszach S, Bigotti MG, Bannister S, Hubner W, Sciandra F, Lamba D, Brancaccio A PLoS One. 2015 May 1;10(5):e0124277. doi: 10.1371/journal.pone.0124277., eCollection 2015. PMID:25932631<ref>PMID:25932631</ref> |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Bigotti, M G]] | ||
[[Category: Bozzi, M]] | [[Category: Bozzi, M]] | ||
| - | [[Category: Bigotti, M.G]] | ||
[[Category: Brancaccio, A]] | [[Category: Brancaccio, A]] | ||
[[Category: Cassetta, A]] | [[Category: Cassetta, A]] | ||
| + | [[Category: Covaceuszach, S]] | ||
| + | [[Category: Lamba, D]] | ||
[[Category: Sciandra, F]] | [[Category: Sciandra, F]] | ||
| - | [[Category: | + | [[Category: Dystroglycanopathy]] |
| + | [[Category: Mutant]] | ||
| + | [[Category: Structural protein]] | ||
Revision as of 12:19, 13 May 2015
The structure of Murine alpha-Dystroglycan T190M mutant N-terminal domain.
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