| 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:https://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:https://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:https://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:https://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:https://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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