8iw0

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the KANK1/liprin-beta1 complex

Structural highlights

8iw0 is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KANK1_HUMAN Inherited congenital spastic tetraplegia. The disease is caused by mutations affecting the gene represented in this entry.

Function

LIPB1_MOUSE May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A (By similarity).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

Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-beta, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.

KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation.,Guo K, Zhang J, Huang P, Xu Y, Pan W, Li K, Chen L, Luo L, Yu W, Chen S, He S, Wei Z, Yu C Cell Rep. 2023 Oct 23;42(11):113321. doi: 10.1016/j.celrep.2023.113321. PMID:37874676^[5]

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

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 K, Zhang J, Huang P, Xu Y, Pan W, Li K, Chen L, Luo L, Yu W, Chen S, He S, Wei Z, Yu C. KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation. Cell Rep. 2023 Oct 23;42(11):113321. PMID:37874676 doi:10.1016/j.celrep.2023.113321

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8iw0"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8iw0 is ON HOLD
+==Crystal structure of the KANK1/liprin-beta1 complex==
+<StructureSection load='8iw0' size='340' side='right'caption='[[8iw0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8iw0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IW0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IW0 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</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=8iw0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8iw0 OCA], [https://pdbe.org/8iw0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8iw0 RCSB], [https://www.ebi.ac.uk/pdbsum/8iw0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8iw0 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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 ==
+[https://www.uniprot.org/uniprot/LIPB1_MOUSE LIPB1_MOUSE] May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A (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 ==
+Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-beta, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.
-Authors:
+KANK1 shapes focal adhesions by orchestrating protein binding, mechanical force sensing, and phase separation.,Guo K, Zhang J, Huang P, Xu Y, Pan W, Li K, Chen L, Luo L, Yu W, Chen S, He S, Wei Z, Yu C Cell Rep. 2023 Oct 23;42(11):113321. doi: 10.1016/j.celrep.2023.113321. PMID:37874676<ref>PMID:37874676</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8iw0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Chen S]]
+[[Category: Wei Z]]
+[[Category: Yu C]]
+[[Category: Zhang J]]

8iw0

From Proteopedia

Current revision

Crystal structure of the KANK1/liprin-beta1 complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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