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| - | [[Image:3aih.png|left|200px]] | |
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| - | <!--
| + | ==Human OS-9 MRH domain complexed with alpha3,alpha6-Man5== |
| - | The line below this paragraph, containing "STRUCTURE_3aih", creates the "Structure Box" on the page.
| + | <StructureSection load='3aih' size='340' side='right'caption='[[3aih]], [[Resolution|resolution]] 2.10Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3aih]] 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=3AIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AIH FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr> |
| - | {{STRUCTURE_3aih| PDB=3aih | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3aih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3aih OCA], [https://pdbe.org/3aih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3aih RCSB], [https://www.ebi.ac.uk/pdbsum/3aih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3aih ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/OS9_HUMAN OS9_HUMAN] Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4.<ref>PMID:17932042</ref> <ref>PMID:18264092</ref> <ref>PMID:18417469</ref> <ref>PMID:19084021</ref> <ref>PMID:19346256</ref> <ref>PMID:21172656</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Misfolded glycoproteins are translocated from endoplasmic reticulum (ER) into the cytosol for proteasome-mediated degradation. A mannose-6-phosphate receptor homology (MRH) domain is commonly identified in a variety of proteins and, in the case of OS-9 and XTP3-B, is involved in glycoprotein ER-associated degradation (ERAD). Trimming of outermost alpha1,2-linked mannose on C-arm of high-mannose-type glycan and binding of processed alpha1,6-linked mannosyl residues by the MRH domain are critical steps in guiding misfolded glycoproteins to enter ERAD. Here we report the crystal structure of a human OS-9 MRH domain (OS-9(MRH)) complexed with alpha3,alpha6-mannopentaose. The OS-9(MRH) has a flattened beta-barrel structure with a characteristic P-type lectin fold and possesses distinctive double tryptophan residues in the oligosaccharide-binding site. Our crystallographic result in conjunction with nuclear magnetic resonance (NMR) spectroscopic and biochemical results provides structural insights into the mechanism whereby OS-9 specifically recognizes Manalpha1,6Manalpha1,6Man residues on the processed C-arm through the continuous double tryptophan (WW) motif. |
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| - | ===Human OS-9 MRH domain complexed with alpha3,alpha6-Man5===
| + | Structural Basis for Oligosaccharide Recognition of Misfolded Glycoproteins by OS-9 in ER-Associated Degradation.,Satoh T, Chen Y, Hu D, Hanashima S, Yamamoto K, Yamaguchi Y Mol Cell. 2010 Dec 22;40(6):905-16. PMID:21172656<ref>PMID:21172656</ref> |
| | | | |
| - | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | <!--
| + | </div> |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_21172656}}, adds the Publication Abstract to the page
| + | <div class="pdbe-citations 3aih" style="background-color:#fffaf0;"></div> |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 21172656 is the PubMed ID number.
| + | == References == |
| - | -->
| + | <references/> |
| - | {{ABSTRACT_PUBMED_21172656}}
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | |
| - | [[3aih]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AIH OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:21172656</ref><references group="xtra"/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Chen, Y.]] | + | [[Category: Large Structures]] |
| - | [[Category: Hanashima, S.]] | + | [[Category: Chen Y]] |
| - | [[Category: Hu, D.]] | + | [[Category: Hanashima S]] |
| - | [[Category: Satoh, T.]] | + | [[Category: Hu D]] |
| - | [[Category: Yamaguchi, Y.]] | + | [[Category: Satoh T]] |
| - | [[Category: Yamamoto, K.]] | + | [[Category: Yamaguchi Y]] |
| | + | [[Category: Yamamoto K]] |
| Structural highlights
Function
OS9_HUMAN Lectin which functions in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). May bind terminally misfolded non-glycosylated proteins as well as improperly folded glycoproteins, retain them in the ER, and possibly transfer them to the ubiquitination machinery and promote their degradation. Possible targets include TRPV4.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Misfolded glycoproteins are translocated from endoplasmic reticulum (ER) into the cytosol for proteasome-mediated degradation. A mannose-6-phosphate receptor homology (MRH) domain is commonly identified in a variety of proteins and, in the case of OS-9 and XTP3-B, is involved in glycoprotein ER-associated degradation (ERAD). Trimming of outermost alpha1,2-linked mannose on C-arm of high-mannose-type glycan and binding of processed alpha1,6-linked mannosyl residues by the MRH domain are critical steps in guiding misfolded glycoproteins to enter ERAD. Here we report the crystal structure of a human OS-9 MRH domain (OS-9(MRH)) complexed with alpha3,alpha6-mannopentaose. The OS-9(MRH) has a flattened beta-barrel structure with a characteristic P-type lectin fold and possesses distinctive double tryptophan residues in the oligosaccharide-binding site. Our crystallographic result in conjunction with nuclear magnetic resonance (NMR) spectroscopic and biochemical results provides structural insights into the mechanism whereby OS-9 specifically recognizes Manalpha1,6Manalpha1,6Man residues on the processed C-arm through the continuous double tryptophan (WW) motif.
Structural Basis for Oligosaccharide Recognition of Misfolded Glycoproteins by OS-9 in ER-Associated Degradation.,Satoh T, Chen Y, Hu D, Hanashima S, Yamamoto K, Yamaguchi Y Mol Cell. 2010 Dec 22;40(6):905-16. PMID:21172656[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang Y, Fu X, Gaiser S, Kottgen M, Kramer-Zucker A, Walz G, Wegierski T. OS-9 regulates the transit and polyubiquitination of TRPV4 in the endoplasmic reticulum. J Biol Chem. 2007 Dec 14;282(50):36561-70. Epub 2007 Oct 11. PMID:17932042 doi:http://dx.doi.org/10.1074/jbc.M703903200
- ↑ Christianson JC, Shaler TA, Tyler RE, Kopito RR. OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nat Cell Biol. 2008 Mar;10(3):272-82. doi: 10.1038/ncb1689. Epub 2008 Feb 10. PMID:18264092 doi:http://dx.doi.org/10.1038/ncb1689
- ↑ Bernasconi R, Pertel T, Luban J, Molinari M. A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal. J Biol Chem. 2008 Jun 13;283(24):16446-54. doi: 10.1074/jbc.M802272200. Epub 2008, Apr 15. PMID:18417469 doi:http://dx.doi.org/10.1074/jbc.M802272200
- ↑ Alcock F, Swanton E. Mammalian OS-9 is upregulated in response to endoplasmic reticulum stress and facilitates ubiquitination of misfolded glycoproteins. J Mol Biol. 2009 Jan 30;385(4):1032-42. doi: 10.1016/j.jmb.2008.11.045. Epub 2008, Nov 30. PMID:19084021 doi:http://dx.doi.org/10.1016/j.jmb.2008.11.045
- ↑ Hosokawa N, Kamiya Y, Kamiya D, Kato K, Nagata K. Human OS-9, a lectin required for glycoprotein endoplasmic reticulum-associated degradation, recognizes mannose-trimmed N-glycans. J Biol Chem. 2009 Jun 19;284(25):17061-8. Epub 2009 Apr 3. PMID:19346256 doi:http://dx.doi.org/M809725200
- ↑ Satoh T, Chen Y, Hu D, Hanashima S, Yamamoto K, Yamaguchi Y. Structural Basis for Oligosaccharide Recognition of Misfolded Glycoproteins by OS-9 in ER-Associated Degradation. Mol Cell. 2010 Dec 22;40(6):905-16. PMID:21172656 doi:10.1016/j.molcel.2010.11.017
- ↑ Satoh T, Chen Y, Hu D, Hanashima S, Yamamoto K, Yamaguchi Y. Structural Basis for Oligosaccharide Recognition of Misfolded Glycoproteins by OS-9 in ER-Associated Degradation. Mol Cell. 2010 Dec 22;40(6):905-16. PMID:21172656 doi:10.1016/j.molcel.2010.11.017
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