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5ky3

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Current revision

mouse POFUT1 in complex with mouse Factor VII EGF1 mutant (T101A) and GDP-fucose

Structural highlights

5ky3 is a 2 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 1.53Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OFUT1_MOUSE Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).^[1] ^[2]

Publication Abstract from PubMed

Protein O-fucosyltransferase 1 (POFUT1) fucosylates the epidermal growth factor (EGF)-like domains found in cell-surface and secreted glycoproteins including Notch and its ligands. Although Notch fucosylation is critical for development, and POFUT1 deficiency leads to human disease, how this enzyme binds and catalyzes the fucosylation of its diverse EGF-like domain substrates has not been determined. Reported here is the X-ray crystal structure of mouse POFUT1 in complex with several EGF-like domains, including EGF12 and EGF26 of Notch. Overall shape complementarity, interactions with invariant atoms of the fucosylation motif and flexible segments on POFUT1 all define its EGF-like-domain binding properties. Using large-scale structural and sequence analysis, we also show that POFUT1 binds EGF-like domains of the hEGF type and that the highly correlated presence of POFUT1 and fucosylatable hEGFs has accompanied animal evolution.

Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1.,Li Z, Han K, Pak JE, Satkunarajah M, Zhou D, Rini JM Nat Chem Biol. 2017 Jul;13(7):757-763. doi: 10.1038/nchembio.2381. Epub 2017 May , 22. PMID:28530709^[3]

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

References

↑ Shi S, Stanley P. Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5234-9. Epub 2003 Apr 15. PMID:12697902 doi:http://dx.doi.org/10.1073/pnas.0831126100
↑ Kim ML, Chandrasekharan K, Glass M, Shi S, Stahl MC, Kaspar B, Stanley P, Martin PT. O-fucosylation of muscle agrin determines its ability to cluster acetylcholine receptors. Mol Cell Neurosci. 2008 Nov;39(3):452-64. doi: 10.1016/j.mcn.2008.07.026. Epub, 2008 Aug 15. PMID:18775496 doi:http://dx.doi.org/10.1016/j.mcn.2008.07.026
↑ Li Z, Han K, Pak JE, Satkunarajah M, Zhou D, Rini JM. Recognition of EGF-like domains by the Notch-modifying O-fucosyltransferase POFUT1. Nat Chem Biol. 2017 Jul;13(7):757-763. doi: 10.1038/nchembio.2381. Epub 2017 May , 22. PMID:28530709 doi:http://dx.doi.org/10.1038/nchembio.2381

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ky3"

Categories: Large Structures | Mus musculus | Li Z | Rini JM

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 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/FA7_MOUSE FA7_MOUSE] Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium (By similarity).
+[https://www.uniprot.org/uniprot/OFUT1_MOUSE OFUT1_MOUSE] Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs).<ref>PMID:12697902</ref> <ref>PMID:18775496</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

5ky3

From Proteopedia

Current revision

mouse POFUT1 in complex with mouse Factor VII EGF1 mutant (T101A) and GDP-fucose

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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