2mk7

Tetra-O-GalNAc glycosylated mucin sequence from alpha dystroglycan mucin domain

spinqualitylabelsall models 2mk7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mk7 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR, 16 models Ligands: A2G, ACE, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease DAG1_HUMAN Defects in DAG1 are the cause of muscular dystrophy-dystroglycanopathy limb-girdle type C7 (MDDGC7) [MIM: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. Function 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. 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. 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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