5n4h

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the D109N mutant of the mouse alpha-Dystroglycan N-terminal region

Structural highlights

5n4h is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.701Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] 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.^[4] ^[5] ^[6] 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).^[7] ^[8] ^[9]

Publication Abstract from PubMed

Dystroglycan (DG) is a highly glycosylated protein complex that links the cytoskeleton with the extracellular matrix, mediating fundamental physiological functions such as mechanical stability of tissues, matrix organization and cell polarity. A crucial role in the glycosylation of the DG alpha subunit is played by its own N-terminal region that is required by the glycosyltransferase LARGE. Alteration in this O-glycosylation deeply impairs the high affinity binding to other extracellular matrix proteins such as laminins. Recently, three missense mutations in the gene encoding DG, mapped in the alpha-DG N-terminal region, were found to be responsible for hypoglycosylated states, causing congenital diseases of different severity referred as primary dystroglycanopaties.To gain insight on the molecular basis of these disorders, we investigated the crystallographic and solution structures of these pathological point mutants, namely V72I, D109N and T190M. Small Angle X-ray Scattering analysis reveals that these mutations affect the structures in solution, altering the distribution between compact and more elongated conformations. These results, supported by biochemical and biophysical assays, point to an altered structural flexibility of the mutant alpha-DG N-terminal region that may have repercussions on its interaction with LARGE and/or other DG-modifying enzymes, eventually reducing their catalytic efficiency.

The effect of the pathological V72I, D109N and T190M missense mutations on the molecular structure of alpha-dystroglycan.,Covaceuszach S, Bozzi M, Bigotti MG, Sciandra F, Konarev PV, Brancaccio A, Cassetta A PLoS One. 2017 Oct 16;12(10):e0186110. doi: 10.1371/journal.pone.0186110., eCollection 2017. PMID:29036200^[10]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Williamson RA, Henry MD, Daniels KJ, Hrstka RF, Lee JC, Sunada Y, Ibraghimov-Beskrovnaya O, Campbell KP. Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice. Hum Mol Genet. 1997 Jun;6(6):831-41. PMID:9175728
↑ Previtali SC, Nodari A, Taveggia C, Pardini C, Dina G, Villa A, Wrabetz L, Quattrini A, Feltri ML. Expression of laminin receptors in schwann cell differentiation: evidence for distinct roles. J Neurosci. 2003 Jul 2;23(13):5520-30. PMID:12843252
↑ Saito F, Moore SA, Barresi R, Henry MD, Messing A, Ross-Barta SE, Cohn RD, Williamson RA, Sluka KA, Sherman DL, Brophy PJ, Schmelzer JD, Low PA, Wrabetz L, Feltri ML, Campbell KP. Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron. 2003 Jun 5;38(5):747-58. PMID:12797959
↑ Williamson RA, Henry MD, Daniels KJ, Hrstka RF, Lee JC, Sunada Y, Ibraghimov-Beskrovnaya O, Campbell KP. Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice. Hum Mol Genet. 1997 Jun;6(6):831-41. PMID:9175728
↑ Previtali SC, Nodari A, Taveggia C, Pardini C, Dina G, Villa A, Wrabetz L, Quattrini A, Feltri ML. Expression of laminin receptors in schwann cell differentiation: evidence for distinct roles. J Neurosci. 2003 Jul 2;23(13):5520-30. PMID:12843252
↑ Saito F, Moore SA, Barresi R, Henry MD, Messing A, Ross-Barta SE, Cohn RD, Williamson RA, Sluka KA, Sherman DL, Brophy PJ, Schmelzer JD, Low PA, Wrabetz L, Feltri ML, Campbell KP. Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron. 2003 Jun 5;38(5):747-58. PMID:12797959
↑ Williamson RA, Henry MD, Daniels KJ, Hrstka RF, Lee JC, Sunada Y, Ibraghimov-Beskrovnaya O, Campbell KP. Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice. Hum Mol Genet. 1997 Jun;6(6):831-41. PMID:9175728
↑ Previtali SC, Nodari A, Taveggia C, Pardini C, Dina G, Villa A, Wrabetz L, Quattrini A, Feltri ML. Expression of laminin receptors in schwann cell differentiation: evidence for distinct roles. J Neurosci. 2003 Jul 2;23(13):5520-30. PMID:12843252
↑ Saito F, Moore SA, Barresi R, Henry MD, Messing A, Ross-Barta SE, Cohn RD, Williamson RA, Sluka KA, Sherman DL, Brophy PJ, Schmelzer JD, Low PA, Wrabetz L, Feltri ML, Campbell KP. Unique role of dystroglycan in peripheral nerve myelination, nodal structure, and sodium channel stabilization. Neuron. 2003 Jun 5;38(5):747-58. PMID:12797959
↑ Covaceuszach S, Bozzi M, Bigotti MG, Sciandra F, Konarev PV, Brancaccio A, Cassetta A. The effect of the pathological V72I, D109N and T190M missense mutations on the molecular structure of alpha-dystroglycan. PLoS One. 2017 Oct 16;12(10):e0186110. doi: 10.1371/journal.pone.0186110., eCollection 2017. PMID:29036200 doi:http://dx.doi.org/10.1371/journal.pone.0186110

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n4h"

@@ Line 3: / Line 3: @@
 <StructureSection load='5n4h' size='340' side='right'caption='[[5n4h]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5n4h]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N4H OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5N4H FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5n4h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N4H FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.701&#8491;</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5n4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4h OCA], [http://pdbe.org/5n4h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n4h RCSB], [http://www.ebi.ac.uk/pdbsum/5n4h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4h ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5n4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n4h OCA], [https://pdbe.org/5n4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n4h RCSB], [https://www.ebi.ac.uk/pdbsum/5n4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n4h ProSAT]</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>
+[https://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 ==
@@ Line 26: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Bigotti, M G]]
+[[Category: Mus musculus]]
-[[Category: Bozzi, M]]
+[[Category: Bigotti MG]]
-[[Category: Brancaccio, A]]
+[[Category: Bozzi M]]
-[[Category: Cassetta, A]]
+[[Category: Brancaccio A]]
-[[Category: Covaceuszach, S]]
+[[Category: Cassetta A]]
-[[Category: Konarev, P V]]
+[[Category: Covaceuszach S]]
-[[Category: Sciandra, F]]
+[[Category: Konarev PV]]
-[[Category: Cell adhesion]]
+[[Category: Sciandra F]]
-[[Category: Dystroglycan]]
-[[Category: Laminin binding]]

5n4h

From Proteopedia

Current revision

Crystal structure of the D109N mutant of the mouse alpha-Dystroglycan N-terminal region

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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