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| | ==Construct of MICAL-1 containing the monooxygenase and calponin homology domains== | | ==Construct of MICAL-1 containing the monooxygenase and calponin homology domains== |
| - | <StructureSection load='4txi' size='340' side='right' caption='[[4txi]], [[Resolution|resolution]] 2.31Å' scene=''> | + | <StructureSection load='4txi' size='340' side='right'caption='[[4txi]], [[Resolution|resolution]] 2.31Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4txi]] is a 1 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=4TXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TXI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4txi]] is a 1 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=4TXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TXI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.309Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4txk|4txk]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Mical1, Mical, Nical ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4txi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txi OCA], [https://pdbe.org/4txi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4txi RCSB], [https://www.ebi.ac.uk/pdbsum/4txi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4txi ProSAT]</span></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=4txi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4txi OCA], [http://pdbe.org/4txi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4txi RCSB], [http://www.ebi.ac.uk/pdbsum/4txi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4txi ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MICA1_MOUSE MICA1_MOUSE]] Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin. Acts by modifying actin subunits through the addition of oxygen to form methionine-sulfoxide, leading to promote actin filament severing and prevent repolymerization. Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments (By similarity). Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. | + | [https://www.uniprot.org/uniprot/MICA1_MOUSE MICA1_MOUSE] Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin. Acts by modifying actin subunits through the addition of oxygen to form methionine-sulfoxide, leading to promote actin filament severing and prevent repolymerization. Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments (By similarity). Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Alqassim, S S]] | + | [[Category: Mus musculus]] |
| - | [[Category: Amzel, L M]] | + | [[Category: Alqassim SS]] |
| - | [[Category: Bianchet, M A]] | + | [[Category: Amzel LM]] |
| - | [[Category: Calponin homology]] | + | [[Category: Bianchet MA]] |
| - | [[Category: Mical]]
| + | |
| - | [[Category: Monooxygenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
MICA1_MOUSE Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin. Acts by modifying actin subunits through the addition of oxygen to form methionine-sulfoxide, leading to promote actin filament severing and prevent repolymerization. Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments (By similarity). Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4.
Publication Abstract from PubMed
MICALs (Molecule Interacting with CasL) are conserved multidomain enzymes essential for cytoskeletal reorganization in nerve development, endocytosis, and apoptosis. In these enzymes, a type-2 calponin homology (CH) domain always follows an N-terminal monooxygenase (MO) domain. Although the CH domain is required for MICAL-1 cellular localization and actin-associated function, its contribution to the modulation of MICAL activity towards actin remains unclear. Here, we present the structure of a fragment of MICAL-1 containing the MO and the CH domains-determined by X-ray crystallography and small angle scattering-as well as kinetics experiments designed to probe the contribution of the CH domain to the actin-modification activity. Our results suggest that the CH domain, which is loosely connected to the MO domain by a flexible linker and is far away from the catalytic site, couples F-actin to the enhancement of redox activity of MICALMO-CH by a cooperative mechanism involving a trans interaction between adjacently bound molecules. Binding cooperativity is also observed in other proteins regulating actin assembly/disassembly dynamics, such as ADF/Cofilins.
Modulation of MICAL Monooxygenase Activity by its Calponin Homology Domain: Structural and Mechanistic Insights.,Alqassim SS, Urquiza M, Borgnia E, Nagib M, Amzel LM, Bianchet MA Sci Rep. 2016 Mar 3;6:22176. doi: 10.1038/srep22176. PMID:26935886[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alqassim SS, Urquiza M, Borgnia E, Nagib M, Amzel LM, Bianchet MA. Modulation of MICAL Monooxygenase Activity by its Calponin Homology Domain: Structural and Mechanistic Insights. Sci Rep. 2016 Mar 3;6:22176. doi: 10.1038/srep22176. PMID:26935886 doi:http://dx.doi.org/10.1038/srep22176
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