View source for 9kbw


==CryoEM structure of microtubule bound with GAS2-GAR domain.==
<StructureSection load='9kbw' size='340' side='right'caption='[[9kbw]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9kbw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9KBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9KBW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=9kbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9kbw OCA], [https://pdbe.org/9kbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9kbw RCSB], [https://www.ebi.ac.uk/pdbsum/9kbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9kbw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GAS2_MOUSE GAS2_MOUSE] May play a role in apoptosis by acting as a cell death substrate for caspases. Is cleaved during apoptosis and the cleaved form induces dramatic rearrangements of the actin cytoskeleton and potent changes in the shape of the affected cells. May play a role in chondrocyte proliferation and differentiation, and in limb myogenesis. May be involved in the regulation of the apoptosis in the interdigital tissues of the developing hindlimb. May be involved in the membrane ruffling process.<ref>PMID:10049561</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The spectraplakin family protein GAS2 was originally identified as a growth arrest-specific protein, and recent studies have revealed its involvement in multiple cellular processes. Its dual interaction with actin filaments and microtubules highlights its essential role in cytoskeletal organization, such as cell division, apoptosis, and possibly tumorigenesis. However, the structural basis of cytoskeletal dynamics regulation by GAS2 remains unclear. In this study, we present cryo-electron microscopy structures of the GAS2 type 3 calponin homology domain (CH3) in complex with F-actin at 2.8 A resolution, thus solving the first type CH3 domain structure bound to F-actin and confirming its actin-binding activity. We also provide the first near-atomic resolution cryo-EM structure of the GAS2-GAR domain bound to microtubules and identify conserved microtubule-binding residues. Our biochemical experiments show that GAS2 promotes microtubule nucleation and polymerization, and that its C-terminal region is essential for dimerization, bundling of both F-actin and microtubules, and microtubule nucleation. As mutations leading to expression of C-terminally truncated GAS2 have been linked to hearing loss, these findings suggest that the disruption of GAS2-dependent cytoskeletal organisation could underlie auditory dysfunction.

Dimerization of GAS2 mediates crosslinking of microtubules and F-actin.,An J, Imasaki T, Narita A, Niwa S, Sasaki R, Makino T, Nitta R, Kikkawa M EMBO J. 2025 May;44(10):2997-3024. doi: 10.1038/s44318-025-00415-2. Epub 2025 Apr , 1. PMID:40169809<ref>PMID:40169809</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9kbw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Sus scrofa]]
[[Category: An J]]
[[Category: Imasaki T]]
[[Category: Kikkawa M]]
[[Category: Makino T]]
[[Category: Narita A]]
[[Category: Nitta R]]
[[Category: Niwa S]]
[[Category: Sasaki R]]