2mk7

<StructureSection load='2mk7' size='340' side='right'caption='[[2mk7]], [[NMR_Ensembles_of_Models | 16 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[2mk7]] is a 1 chain structure. 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='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></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>

== 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>

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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 2mk7" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Borgert, A]]

[[Category: Live, D]]

[[Category: Tn antigen]]