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| | <StructureSection load='6nax' size='340' side='right'caption='[[6nax]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='6nax' size='340' side='right'caption='[[6nax]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nax]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NAX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nax]] is a 2 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=6NAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NAX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.551Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Myoc, Tigr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nax OCA], [http://pdbe.org/6nax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nax RCSB], [http://www.ebi.ac.uk/pdbsum/6nax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nax ProSAT]</span></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=6nax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nax OCA], [https://pdbe.org/6nax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nax RCSB], [https://www.ebi.ac.uk/pdbsum/6nax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nax ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MYOC_MOUSE MYOC_MOUSE]] Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling (By similarity). Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling (PubMed:23629661). Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling (PubMed:23897819). Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex (PubMed:22371502). Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork (By similarity).[UniProtKB:Q99972]<ref>PMID:22371502</ref> <ref>PMID:23629661</ref> <ref>PMID:23897819</ref> | + | [https://www.uniprot.org/uniprot/MYOC_MOUSE MYOC_MOUSE] Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling (By similarity). Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling (PubMed:23629661). Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling (PubMed:23897819). Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex (PubMed:22371502). Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork (By similarity).[UniProtKB:Q99972]<ref>PMID:22371502</ref> <ref>PMID:23629661</ref> <ref>PMID:23897819</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hill, S E]] | + | [[Category: Hill SE]] |
| - | [[Category: Lieberman, R L]] | + | [[Category: Lieberman RL]] |
| - | [[Category: Patterson-Orazem, A C]] | + | [[Category: Patterson-Orazem AC]] |
| - | [[Category: Murine]]
| + | |
| - | [[Category: Olfactomedin]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
MYOC_MOUSE Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling (By similarity). Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling (PubMed:23629661). Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling (PubMed:23897819). Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex (PubMed:22371502). Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork (By similarity).[UniProtKB:Q99972][1] [2] [3]
Publication Abstract from PubMed
Mutations in myocilin, predominantly within its olfactomedin (OLF) domain, are causative for the heritable form of open angle glaucoma in humans. Surprisingly, mice expressing Tyr423His mutant myocilin, corresponding to a severe glaucoma-causing mutation (Tyr437His) in human subjects, exhibit a weak, if any, glaucoma phenotype. To address possible protein-level discrepancies between mouse and human OLFs, which might lead to this outcome, biophysical properties of mouse OLF were characterized for comparison with those of human OLF. The 1.55 A resolution crystal structure of mouse OLF reveals an asymmetric 5-bladed beta-propeller that is nearly indistinguishable from previous structures of human OLF. Wild-type and selected mutant mouse OLFs mirror thermal stabilities of their human OLF counterparts, including characteristic stabilization in the presence of calcium. Mouse OLF forms thioflavin T-positive aggregates with a similar end-point morphology as human OLF, but amyloid aggregation kinetic rates of mouse OLF are faster than human OLF. Simulations and experiments support the interpretation that kinetics of mouse OLF are faster because of a decreased charge repulsion arising from more neutral surface electrostatics. Taken together, phenotypic differences observed in mouse and human studies of mutant myocilin could be a function of aggregation kinetics rates, which would alter the lifetime of putatively toxic protofibrillar intermediates.
Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice.,Patterson-Orazem AC, Hill SE, Wang Y, Dominic IM, Hall CK, Lieberman RL Biochemistry. 2019 Mar 12. doi: 10.1021/acs.biochem.8b01309. PMID:30802039[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Joe MK, Kee C, Tomarev SI. Myocilin interacts with syntrophins and is member of dystrophin-associated protein complex. J Biol Chem. 2012 Apr 13;287(16):13216-27. doi: 10.1074/jbc.M111.224063. Epub, 2012 Feb 25. PMID:22371502 doi:http://dx.doi.org/10.1074/jbc.M111.224063
- ↑ Kwon HS, Johnson TV, Tomarev SI. Myocilin stimulates osteogenic differentiation of mesenchymal stem cells through mitogen-activated protein kinase signaling. J Biol Chem. 2013 Jun 7;288(23):16882-94. doi: 10.1074/jbc.M112.422972. Epub 2013, Apr 29. PMID:23629661 doi:http://dx.doi.org/10.1074/jbc.M112.422972
- ↑ Kwon HS, Johnson TV, Joe MK, Abu-Asab M, Zhang J, Chan CC, Tomarev SI. Myocilin mediates myelination in the peripheral nervous system through ErbB2/3 signaling. J Biol Chem. 2013 Sep 13;288(37):26357-71. doi: 10.1074/jbc.M112.446138. Epub, 2013 Jul 29. PMID:23897819 doi:http://dx.doi.org/10.1074/jbc.M112.446138
- ↑ Patterson-Orazem AC, Hill SE, Wang Y, Dominic IM, Hall CK, Lieberman RL. Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice. Biochemistry. 2019 Mar 12. doi: 10.1021/acs.biochem.8b01309. PMID:30802039 doi:http://dx.doi.org/10.1021/acs.biochem.8b01309
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