4wiq

From Proteopedia

(Difference between revisions)

Current revision

The structure of Murine alpha-Dystroglycan T190M mutant N-terminal domain.

Structural highlights

4wiq 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 1.59Å
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

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 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^[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
↑ Bozzi M, Cassetta A, Covaceuszach S, Bigotti MG, Bannister S, Hubner W, Sciandra F, Lamba D, Brancaccio A. The Structure of the T190M Mutant of Murine alpha-Dystroglycan at High Resolution: Insight into the Molecular Basis of a Primary Dystroglycanopathy. PLoS One. 2015 May 1;10(5):e0124277. doi: 10.1371/journal.pone.0124277., eCollection 2015. PMID:25932631 doi:http://dx.doi.org/10.1371/journal.pone.0124277

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/4wiq"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4wiq is ON HOLD  until Paper Publication
+==The structure of Murine alpha-Dystroglycan T190M mutant N-terminal domain.==
+<StructureSection load='4wiq' size='340' side='right'caption='[[4wiq]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4wiq]] 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=4WIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WIQ FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4wiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wiq OCA], [https://pdbe.org/4wiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wiq RCSB], [https://www.ebi.ac.uk/pdbsum/4wiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wiq ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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 ==
+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.
-Authors: Brancaccio, A., Lamba, D., Cassetta, A., Bozzi, M., Covaceuszach, S., Sciandra, F., Bigotti, M.G.
+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>
-Description: The structure of Murine alpha-Dystroglycan T190M mutant N-terminal domain.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4wiq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dystroglycan|Dystroglycan]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Bigotti MG]]
+[[Category: Bozzi M]]
+[[Category: Brancaccio A]]
+[[Category: Cassetta A]]
+[[Category: Covaceuszach S]]
+[[Category: Lamba D]]
+[[Category: Sciandra F]]

4wiq

From Proteopedia

Current revision

The structure of Murine alpha-Dystroglycan T190M mutant N-terminal domain.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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