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| | ==Structure of the KANK1 ankyrin domain in complex with KIF21A peptide== | | ==Structure of the KANK1 ankyrin domain in complex with KIF21A peptide== |
| - | <StructureSection load='5ybu' size='340' side='right' caption='[[5ybu]], [[Resolution|resolution]] 1.89Å' scene=''> | + | <StructureSection load='5ybu' size='340' side='right'caption='[[5ybu]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ybu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YBU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YBU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ybu]] is a 2 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=5YBU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YBU FirstGlance]. <br> |
| - | </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=5ybu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybu OCA], [http://pdbe.org/5ybu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ybu RCSB], [http://www.ebi.ac.uk/pdbsum/5ybu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybu ProSAT]</span></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]] 1.89Å</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=5ybu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybu OCA], [https://pdbe.org/5ybu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ybu RCSB], [https://www.ebi.ac.uk/pdbsum/5ybu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/KANK1_HUMAN KANK1_HUMAN]] Inherited congenital spastic tetraplegia. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/KI21A_HUMAN KI21A_HUMAN]] Congenital fibrosis of extraocular muscles. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/KANK1_HUMAN KANK1_HUMAN] Inherited congenital spastic tetraplegia. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KANK1_HUMAN KANK1_HUMAN]] Involved in the control of cytoskeleton formation by regulating actin polymerization. Inhibits actin fiber formation and cell migration. Inhibits RhoA activity; the function involves phosphorylation through PI3K/Akt signaling and may depend on the competetive interaction with 14-3-3 adapter proteins to sequester them from active complexes. Inhibits the formation of lamellipodia but not of filopodia; the function may depend on the competetive interaction with BAIAP2 to block its association with activated RAC1. Inhibits fibronectin-mediated cell spreading; the function is partially mediated by BAIAP2. Inhibits neurite outgrowth. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. In the nucleus, is involved in beta-catenin-dependent activation of transcription. Potential tumor suppressor for renal cell carcinoma.<ref>PMID:16968744</ref> <ref>PMID:18458160</ref> <ref>PMID:19171758</ref> <ref>PMID:22084092</ref> [[http://www.uniprot.org/uniprot/KI21A_HUMAN KI21A_HUMAN]] Microtubule-binding motor protein probably involved in neuronal axonal transport. In vitro, has a plus-end directed motor activity (By similarity). | + | [https://www.uniprot.org/uniprot/KANK1_HUMAN KANK1_HUMAN] Involved in the control of cytoskeleton formation by regulating actin polymerization. Inhibits actin fiber formation and cell migration. Inhibits RhoA activity; the function involves phosphorylation through PI3K/Akt signaling and may depend on the competetive interaction with 14-3-3 adapter proteins to sequester them from active complexes. Inhibits the formation of lamellipodia but not of filopodia; the function may depend on the competetive interaction with BAIAP2 to block its association with activated RAC1. Inhibits fibronectin-mediated cell spreading; the function is partially mediated by BAIAP2. Inhibits neurite outgrowth. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. In the nucleus, is involved in beta-catenin-dependent activation of transcription. Potential tumor suppressor for renal cell carcinoma.<ref>PMID:16968744</ref> <ref>PMID:18458160</ref> <ref>PMID:19171758</ref> <ref>PMID:22084092</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | A well-controlled microtubule organization is essential for intracellular transport, cytoskeleton maintenance, and cell development. KN motif and ankyrin repeat domain-containing protein 1 (KANK1), a member of KANK family, could recruit kinesin family member 21A (KIF21A) to the cell cortex to control microtubule growth via its C-terminal ankyrin domain. However, how the KANK1 ankyrin domain recognizes KIF21A and whether other KANK proteins can also bind KIF21A remain unknown. Here, using a combination of structural, site-directed mutagenesis, and biochemical studies, we found that a stretch of ~22 amino acids in KIF21A is sufficient for binding to KANK1 and its close homolog KANK2, and solved the complex structure of the KIF21A peptide with either the KANK1 ankyrin domain or the KANK2 ankyrin domain. In each complex, KIF21A is recognized by two distinct pockets of the ankyrin domain and adopts helical conformations upon binding to the ankyrin domain. The elucidated KANK structures may advance our understanding the role of KANK1 as a scaffolding molecule in controlling microtubule growth at the cell periphery. |
| | + | |
| | + | Structural basis for the recognition of kinesin family member 21A (KIF21A) by the ankyrin domains of KANK1 and KANK2 proteins.,Guo Q, Liao S, Zhu Z, Li Y, Li F, Xu C J Biol Chem. 2017 Nov 28. pii: M117.817494. doi: 10.1074/jbc.M117.817494. PMID:29183992<ref>PMID:29183992</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5ybu" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ankyrin repeat domain-containing protein 3D structures|Ankyrin repeat domain-containing protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Guo, Q]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Liao, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Min, J]] | + | [[Category: Guo Q]] |
| - | [[Category: Structural genomic]] | + | [[Category: Liao S]] |
| - | [[Category: Xu, C]] | + | [[Category: Min J]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Xu C]] |
| Structural highlights
Disease
KANK1_HUMAN Inherited congenital spastic tetraplegia. The disease is caused by mutations affecting the gene represented in this entry.
Function
KANK1_HUMAN Involved in the control of cytoskeleton formation by regulating actin polymerization. Inhibits actin fiber formation and cell migration. Inhibits RhoA activity; the function involves phosphorylation through PI3K/Akt signaling and may depend on the competetive interaction with 14-3-3 adapter proteins to sequester them from active complexes. Inhibits the formation of lamellipodia but not of filopodia; the function may depend on the competetive interaction with BAIAP2 to block its association with activated RAC1. Inhibits fibronectin-mediated cell spreading; the function is partially mediated by BAIAP2. Inhibits neurite outgrowth. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. In the nucleus, is involved in beta-catenin-dependent activation of transcription. Potential tumor suppressor for renal cell carcinoma.[1] [2] [3] [4]
Publication Abstract from PubMed
A well-controlled microtubule organization is essential for intracellular transport, cytoskeleton maintenance, and cell development. KN motif and ankyrin repeat domain-containing protein 1 (KANK1), a member of KANK family, could recruit kinesin family member 21A (KIF21A) to the cell cortex to control microtubule growth via its C-terminal ankyrin domain. However, how the KANK1 ankyrin domain recognizes KIF21A and whether other KANK proteins can also bind KIF21A remain unknown. Here, using a combination of structural, site-directed mutagenesis, and biochemical studies, we found that a stretch of ~22 amino acids in KIF21A is sufficient for binding to KANK1 and its close homolog KANK2, and solved the complex structure of the KIF21A peptide with either the KANK1 ankyrin domain or the KANK2 ankyrin domain. In each complex, KIF21A is recognized by two distinct pockets of the ankyrin domain and adopts helical conformations upon binding to the ankyrin domain. The elucidated KANK structures may advance our understanding the role of KANK1 as a scaffolding molecule in controlling microtubule growth at the cell periphery.
Structural basis for the recognition of kinesin family member 21A (KIF21A) by the ankyrin domains of KANK1 and KANK2 proteins.,Guo Q, Liao S, Zhu Z, Li Y, Li F, Xu C J Biol Chem. 2017 Nov 28. pii: M117.817494. doi: 10.1074/jbc.M117.817494. PMID:29183992[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang Y, Kakinuma N, Zhu Y, Kiyama R. Nucleo-cytoplasmic shuttling of human Kank protein accompanies intracellular translocation of beta-catenin. J Cell Sci. 2006 Oct 1;119(Pt 19):4002-10. doi: 10.1242/jcs.03169. Epub 2006 Sep , 12. PMID:16968744 doi:http://dx.doi.org/10.1242/jcs.03169
- ↑ Kakinuma N, Roy BC, Zhu Y, Wang Y, Kiyama R. Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K-Akt signaling. J Cell Biol. 2008 May 5;181(3):537-49. doi: 10.1083/jcb.200707022. PMID:18458160 doi:http://dx.doi.org/10.1083/jcb.200707022
- ↑ Roy BC, Kakinuma N, Kiyama R. Kank attenuates actin remodeling by preventing interaction between IRSp53 and Rac1. J Cell Biol. 2009 Jan 26;184(2):253-67. doi: 10.1083/jcb.200805147. PMID:19171758 doi:http://dx.doi.org/10.1083/jcb.200805147
- ↑ Li CC, Kuo JC, Waterman CM, Kiyama R, Moss J, Vaughan M. Effects of brefeldin A-inhibited guanine nucleotide-exchange (BIG) 1 and KANK1 proteins on cell polarity and directed migration during wound healing. Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19228-33. doi:, 10.1073/pnas.1117011108. Epub 2011 Nov 14. PMID:22084092 doi:10.1073/pnas.1117011108
- ↑ Guo Q, Liao S, Zhu Z, Li Y, Li F, Xu C. Structural basis for the recognition of kinesin family member 21A (KIF21A) by the ankyrin domains of KANK1 and KANK2 proteins. J Biol Chem. 2017 Nov 28. pii: M117.817494. doi: 10.1074/jbc.M117.817494. PMID:29183992 doi:http://dx.doi.org/10.1074/jbc.M117.817494
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