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| | <StructureSection load='4z6g' size='340' side='right'caption='[[4z6g]], [[Resolution|resolution]] 2.65Å' scene=''> | | <StructureSection load='4z6g' size='340' side='right'caption='[[4z6g]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4z6g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Z6G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z6G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4z6g]] is a 1 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=4Z6G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z6G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.654Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MACF1, ABP620, ACF7, KIAA0465, KIAA1251 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4z6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z6g OCA], [http://pdbe.org/4z6g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z6g RCSB], [http://www.ebi.ac.uk/pdbsum/4z6g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z6g 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=4z6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z6g OCA], [https://pdbe.org/4z6g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z6g RCSB], [https://www.ebi.ac.uk/pdbsum/4z6g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z6g ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MACF1_HUMAN MACF1_HUMAN]] Isoform 2 is a F-actin-binding protein which may play a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane. Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics. May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4. Plays a key role in wound healing and epidermal cell migration. Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate MT dynamics and polarize hair follicle stem cells (By similarity).<ref>PMID:15265687</ref> <ref>PMID:20937854</ref> | + | [https://www.uniprot.org/uniprot/MACF1_HUMAN MACF1_HUMAN] Isoform 2 is a F-actin-binding protein which may play a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane. Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics. May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4. Plays a key role in wound healing and epidermal cell migration. Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate MT dynamics and polarize hair follicle stem cells (By similarity).<ref>PMID:15265687</ref> <ref>PMID:20937854</ref> |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Yang, F]] | + | [[Category: Yang F]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cell migration]]
| + | |
| - | [[Category: Cytoskeleton]]
| + | |
| - | [[Category: Focal adhesion]]
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| - | [[Category: Microtubule]]
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| Structural highlights
Function
MACF1_HUMAN Isoform 2 is a F-actin-binding protein which may play a role in cross-linking actin to other cytoskeletal proteins and also binds to microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Acts as a positive regulator of Wnt receptor signaling pathway and is involved in the translocation of AXIN1 and its associated complex (composed of APC, CTNNB1 and GSK3B) from the cytoplasm to the cell membrane. Has actin-regulated ATPase activity and is essential for controlling focal adhesions (FAs) assembly and dynamics. May play role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with GOLGA4. Plays a key role in wound healing and epidermal cell migration. Required for efficient upward migration of bulge cells in response to wounding and this function is primarily rooted in its ability to coordinate MT dynamics and polarize hair follicle stem cells (By similarity).[1] [2]
Publication Abstract from PubMed
Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7's NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Together, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement.
In vivo epidermal migration requires focal adhesion targeting of ACF7.,Yue J, Zhang Y, Liang WG, Gou X, Lee P, Liu H, Lyu W, Tang WJ, Chen SY, Yang F, Liang H, Wu X Nat Commun. 2016 May 24;7:11692. doi: 10.1038/ncomms11692. PMID:27216888[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kakinuma T, Ichikawa H, Tsukada Y, Nakamura T, Toh BH. Interaction between p230 and MACF1 is associated with transport of a glycosyl phosphatidyl inositol-anchored protein from the Golgi to the cell periphery. Exp Cell Res. 2004 Aug 15;298(2):388-98. PMID:15265687 doi:http://dx.doi.org/10.1016/j.yexcr.2004.04.047
- ↑ Zaoui K, Benseddik K, Daou P, Salaun D, Badache A. ErbB2 receptor controls microtubule capture by recruiting ACF7 to the plasma membrane of migrating cells. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18517-22. doi:, 10.1073/pnas.1000975107. Epub 2010 Oct 11. PMID:20937854 doi:10.1073/pnas.1000975107
- ↑ Yue J, Zhang Y, Liang WG, Gou X, Lee P, Liu H, Lyu W, Tang WJ, Chen SY, Yang F, Liang H, Wu X. In vivo epidermal migration requires focal adhesion targeting of ACF7. Nat Commun. 2016 May 24;7:11692. doi: 10.1038/ncomms11692. PMID:27216888 doi:http://dx.doi.org/10.1038/ncomms11692
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