9e1t: Difference between revisions

Latest revision as of 06:25, 12 February 2025

CryoEM structure of LARGE1 bound to UDP

Structural highlights

9e1t is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:	MN, UDP
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

LARG1_HUMAN Congenital muscular dystrophy with intellectual disability;Walker-Warburg syndrome;Muscle-eye-brain disease. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

LARG1_HUMAN Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity (PubMed:15661757, PubMed:15752776, PubMed:21987822, PubMed:22223806, PubMed:23125099, PubMed:25279697, PubMed:25279699). Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (PubMed:22223806, PubMed:23125099, PubMed:25138275, PubMed:25279697, PubMed:25279699, PubMed:32975514). Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide primer (PubMed:21987822). Plays a key role in skeletal muscle function and regeneration (By similarity).[UniProtKB:Q9Z1M7]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9]

References

↑ Brockington M, Torelli S, Prandini P, Boito C, Dolatshad NF, Longman C, Brown SC, Muntoni F. Localization and functional analysis of the LARGE family of glycosyltransferases: significance for muscular dystrophy. Hum Mol Genet. 2005 Mar 1;14(5):657-65. Epub 2005 Jan 20. PMID:15661757 doi:https://dx.doi.org/ddi062
↑ Fujimura K, Sawaki H, Sakai T, Hiruma T, Nakanishi N, Sato T, Ohkura T, Narimatsu H. LARGE2 facilitates the maturation of alpha-dystroglycan more effectively than LARGE. Biochem Biophys Res Commun. 2005 Apr 15;329(3):1162-71. PMID:15752776 doi:https://dx.doi.org/S0006-291X(05)00336-0
↑ Hara Y, Kanagawa M, Kunz S, Yoshida-Moriguchi T, Satz JS, Kobayashi YM, Zhu Z, Burden SJ, Oldstone MB, Campbell KP. Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17426-31. doi: , 10.1073/pnas.1114836108. Epub 2011 Oct 10. PMID:21987822 doi:https://dx.doi.org/10.1073/pnas.1114836108
↑ Inamori K, Yoshida-Moriguchi T, Hara Y, Anderson ME, Yu L, Campbell KP. Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science. 2012 Jan 6;335(6064):93-6. doi: 10.1126/science.1214115. PMID:22223806 doi:https://dx.doi.org/10.1126/science.1214115
↑ Inamori K, Hara Y, Willer T, Anderson ME, Zhu Z, Yoshida-Moriguchi T, Campbell KP. Xylosyl- and glucuronyltransferase functions of LARGE in alpha-dystroglycan modification are conserved in LARGE2. Glycobiology. 2013 Mar;23(3):295-302. doi: 10.1093/glycob/cws152. Epub 2012 Nov , 2. PMID:23125099 doi:https://dx.doi.org/10.1093/glycob/cws152
↑ Inamori K, Willer T, Hara Y, Venzke D, Anderson ME, Clarke NF, Guicheney P, Bonnemann CG, Moore SA, Campbell KP. Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of alpha-dystroglycan in cells and tissues. J Biol Chem. 2014 Oct 10;289(41):28138-48. doi: 10.1074/jbc.M114.597831. Epub , 2014 Aug 19. PMID:25138275 doi:https://dx.doi.org/10.1074/jbc.M114.597831
↑ Praissman JL, Live DH, Wang S, Ramiah A, Chinoy ZS, Boons GJ, Moremen KW, Wells L. B4GAT1 is the priming enzyme for the LARGE-dependent functional glycosylation of alpha-dystroglycan. Elife. 2014 Oct 3;3. doi: 10.7554/eLife.03943. PMID:25279697 doi:https://dx.doi.org/10.7554/eLife.03943
↑ Willer T, Inamori K, Venzke D, Harvey C, Morgensen G, Hara Y, Beltran Valero de Bernabe D, Yu L, Wright KM, Campbell KP. The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated alpha-dystroglycan functional glycosylation. Elife. 2014 Oct 3;3. doi: 10.7554/eLife.03941. PMID:25279699 doi:https://dx.doi.org/10.7554/eLife.03941
↑ Walimbe AS, Okuma H, Joseph S, Yang T, Yonekawa T, Hord JM, Venzke D, Anderson ME, Torelli S, Manzur A, Devereaux M, Cuellar M, Prouty S, Ocampo Landa S, Yu L, Xiao J, Dixon JE, Muntoni F, Campbell KP. POMK regulates dystroglycan function via LARGE1-mediated elongation of matriglycan. Elife. 2020 Sep 25;9:e61388. doi: 10.7554/eLife.61388. PMID:32975514 doi:https://dx.doi.org/10.7554/eLife.61388

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OCA

[1] Brockington M, Torelli S, Prandini P, Boito C, Dolatshad NF, Longman C, Brown SC, Muntoni F. Localization and functional analysis of the LARGE family of glycosyltransferases: significance for muscular dystrophy. Hum Mol Genet. 2005 Mar 1;14(5):657-65. Epub 2005 Jan 20. PMID:15661757 doi:https://dx.doi.org/ddi062

[2] Fujimura K, Sawaki H, Sakai T, Hiruma T, Nakanishi N, Sato T, Ohkura T, Narimatsu H. LARGE2 facilitates the maturation of alpha-dystroglycan more effectively than LARGE. Biochem Biophys Res Commun. 2005 Apr 15;329(3):1162-71. PMID:15752776 doi:https://dx.doi.org/S0006-291X(05)00336-0

[3] Hara Y, Kanagawa M, Kunz S, Yoshida-Moriguchi T, Satz JS, Kobayashi YM, Zhu Z, Burden SJ, Oldstone MB, Campbell KP. Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection. Proc Natl Acad Sci U S A. 2011 Oct 18;108(42):17426-31. doi: , 10.1073/pnas.1114836108. Epub 2011 Oct 10. PMID:21987822 doi:https://dx.doi.org/10.1073/pnas.1114836108

[4] Inamori K, Yoshida-Moriguchi T, Hara Y, Anderson ME, Yu L, Campbell KP. Dystroglycan function requires xylosyl- and glucuronyltransferase activities of LARGE. Science. 2012 Jan 6;335(6064):93-6. doi: 10.1126/science.1214115. PMID:22223806 doi:https://dx.doi.org/10.1126/science.1214115

[5] Inamori K, Hara Y, Willer T, Anderson ME, Zhu Z, Yoshida-Moriguchi T, Campbell KP. Xylosyl- and glucuronyltransferase functions of LARGE in alpha-dystroglycan modification are conserved in LARGE2. Glycobiology. 2013 Mar;23(3):295-302. doi: 10.1093/glycob/cws152. Epub 2012 Nov , 2. PMID:23125099 doi:https://dx.doi.org/10.1093/glycob/cws152

[6] Inamori K, Willer T, Hara Y, Venzke D, Anderson ME, Clarke NF, Guicheney P, Bonnemann CG, Moore SA, Campbell KP. Endogenous glucuronyltransferase activity of LARGE or LARGE2 required for functional modification of alpha-dystroglycan in cells and tissues. J Biol Chem. 2014 Oct 10;289(41):28138-48. doi: 10.1074/jbc.M114.597831. Epub , 2014 Aug 19. PMID:25138275 doi:https://dx.doi.org/10.1074/jbc.M114.597831

[7] Praissman JL, Live DH, Wang S, Ramiah A, Chinoy ZS, Boons GJ, Moremen KW, Wells L. B4GAT1 is the priming enzyme for the LARGE-dependent functional glycosylation of alpha-dystroglycan. Elife. 2014 Oct 3;3. doi: 10.7554/eLife.03943. PMID:25279697 doi:https://dx.doi.org/10.7554/eLife.03943

[8] Willer T, Inamori K, Venzke D, Harvey C, Morgensen G, Hara Y, Beltran Valero de Bernabe D, Yu L, Wright KM, Campbell KP. The glucuronyltransferase B4GAT1 is required for initiation of LARGE-mediated alpha-dystroglycan functional glycosylation. Elife. 2014 Oct 3;3. doi: 10.7554/eLife.03941. PMID:25279699 doi:https://dx.doi.org/10.7554/eLife.03941

[9] Walimbe AS, Okuma H, Joseph S, Yang T, Yonekawa T, Hord JM, Venzke D, Anderson ME, Torelli S, Manzur A, Devereaux M, Cuellar M, Prouty S, Ocampo Landa S, Yu L, Xiao J, Dixon JE, Muntoni F, Campbell KP. POMK regulates dystroglycan function via LARGE1-mediated elongation of matriglycan. Elife. 2020 Sep 25;9:e61388. doi: 10.7554/eLife.61388. PMID:32975514 doi:https://dx.doi.org/10.7554/eLife.61388

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9e1t is ON HOLD  until Paper Publication
+==CryoEM structure of LARGE1 bound to UDP==
+<StructureSection load='9e1t' size='340' side='right'caption='[[9e1t]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
-Authors: Joesph, S., Spellmon, N., Campbell, K.P.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9e1t]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9E1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9E1T FirstGlance]. <br>
-Description: CryoEM structure of LARGE1 bound to UDP
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
-[[Category: Campbell, K.P]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9e1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9e1t OCA], [https://pdbe.org/9e1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9e1t RCSB], [https://www.ebi.ac.uk/pdbsum/9e1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9e1t ProSAT]</span></td></tr>
-[[Category: Joesph, S]]
+</table>
-[[Category: Spellmon, N]]
+== Disease ==
+[https://www.uniprot.org/uniprot/LARG1_HUMAN LARG1_HUMAN] Congenital muscular dystrophy with intellectual disability;Walker-Warburg syndrome;Muscle-eye-brain disease. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/LARG1_HUMAN LARG1_HUMAN] Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity (PubMed:15661757, PubMed:15752776, PubMed:21987822, PubMed:22223806, PubMed:23125099, PubMed:25279697, PubMed:25279699). Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (PubMed:22223806, PubMed:23125099, PubMed:25138275, PubMed:25279697, PubMed:25279699, PubMed:32975514). Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide primer (PubMed:21987822). Plays a key role in skeletal muscle function and regeneration (By similarity).[UniProtKB:Q9Z1M7]<ref>PMID:15661757</ref> <ref>PMID:15752776</ref> <ref>PMID:21987822</ref> <ref>PMID:22223806</ref> <ref>PMID:23125099</ref> <ref>PMID:25138275</ref> <ref>PMID:25279697</ref> <ref>PMID:25279699</ref> <ref>PMID:32975514</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Campbell KP]]
+[[Category: Joesph S]]
+[[Category: Spellmon N]]

9e1t: Difference between revisions

Latest revision as of 06:25, 12 February 2025

CryoEM structure of LARGE1 bound to UDP

Structural highlights

Disease

Function

References

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