2mk7: Difference between revisions
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New page: '''Unreleased structure''' The entry 2mk7 is ON HOLD Authors: Live, D., Borgert, A. Description: Tetra-O-GalNAc glycosylated mucin sequence from alpha dystroglycan mucin domain |
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The | ==Tetra-O-GalNAc glycosylated mucin sequence from alpha dystroglycan mucin domain== | ||
<StructureSection load='2mk7' size='340' side='right'caption='[[2mk7]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2mk7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MK7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MK7 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 16 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2G:N-ACETYL-2-DEOXY-2-AMINO-GALACTOSE'>A2G</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mk7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mk7 OCA], [https://pdbe.org/2mk7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mk7 RCSB], [https://www.ebi.ac.uk/pdbsum/2mk7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mk7 ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/DAG1_HUMAN DAG1_HUMAN] Defects in DAG1 are the cause of muscular dystrophy-dystroglycanopathy limb-girdle type C7 (MDDGC7) [MIM:[https://omim.org/entry/613818 613818]. An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with mental retardation without structural brain anomalies. Note=MDDGC7 is caused by DAG1 mutations that interfere with normal post-translational processing, resulting in defective DAG1 glycosylation and impaired interactions with extracellular-matrix components. Other muscular dystrophy-dystroglycanopathies are caused by defects in enzymes involved in protein O-glycosylation.<ref>PMID:21388311</ref> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/DAG1_HUMAN DAG1_HUMAN] The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.<ref>PMID:9851927</ref> <ref>PMID:11724572</ref> <ref>PMID:16254364</ref> <ref>PMID:17360738</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 acts as a receptor for M.leprae in peripheral nerve Schwann cells but only in the presence of the G-domain of LAMA2, and for lymphocytic choriomeningitis virus, Old World Lassa fever virus, and clade C New World arenaviruses.<ref>PMID:9851927</ref> <ref>PMID:11724572</ref> <ref>PMID:16254364</ref> <ref>PMID:17360738</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.<ref>PMID:9851927</ref> <ref>PMID:11724572</ref> <ref>PMID:16254364</ref> <ref>PMID:17360738</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We have carried out a comparative study of the conformational impact of modifications to threonine residues of either alpha-O-Man or alpha-O-GalNAc in the context of a sequence from the mucin-like region of alpha-dystroglycan. Both such modifications can coexist in this domain of the glycoprotein. Solution NMR experiments and molecular dynamics calculations were employed. Comparing the results for an unmodified peptide Ac- PPTTTTKKP-NH2 sequence from alpha-dystroglycan, and glycoconjugates with either modification on the Ts, we find that the impact of the alpha-O-Man modification on the peptide scaffold is quite limited, while that of the alpha-O-GalNAc is more profound. The results for the alpha-O-GalNAc glycoconjugate are consistent with what has been seen earlier in other systems. Further examination of the NMR-based structure and the MD results suggest a more extensive network of hydrogen bond interactions within the alpha-O-GalNAc-threonine residue than has been previously appreciated, which influences the properties of the protein backbone. The conformational effects are relevant to the mechanical properties of alpha-dystroglycan. | |||
Contrasting the conformational effects of alpha-O-GalNAc and alpha-O-Man glycan protein modifications and their impact on the mucin-like region of alpha-dystroglycan.,Borgert A, Foley BL, Live D Glycobiology. 2021 Jun 3;31(5):649-661. doi: 10.1093/glycob/cwaa112. PMID:33295623<ref>PMID:33295623</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2mk7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Borgert A]] | |||
[[Category: Live D]] | |||
