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{{STRUCTURE_4ci8|  PDB=4ci8  |  SCENE=  }}
===Crystal structure of the tandem atypical beta-propeller domain of EML1===
{{ABSTRACT_PUBMED_24706829}}


==Function==
==Crystal structure of the tandem atypical beta-propeller domain of EML1==
[[http://www.uniprot.org/uniprot/EMAL1_HUMAN EMAL1_HUMAN]] May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic (By similarity).  
<StructureSection load='4ci8' size='340' side='right'caption='[[4ci8]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ci8]] 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=4CI8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CI8 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4ci8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ci8 OCA], [https://pdbe.org/4ci8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ci8 RCSB], [https://www.ebi.ac.uk/pdbsum/4ci8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ci8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/EMAL1_HUMAN EMAL1_HUMAN] May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Proteins of the echinoderm microtubule-associated protein (EMAP)-like (EML) family contribute to formation of the mitotic spindle and interphase microtubule network. They contain a unique hydrophobic EML protein (HELP) motif and a variable number of WD40 repeats. Recurrent gene rearrangements in nonsmall cell lung cancer fuse EML4 to anaplastic lymphoma kinase (ALK), causing expression of several fusion oncoprotein variants. We have determined a 2.6-A crystal structure of the representative approximately 70-kDa core of EML1, revealing an intimately associated pair of beta-propellers, which we term a TAPE (tandem atypical propeller in EMLs) domain. One propeller is highly atypical, having a discontinuous subdomain unrelated to a WD40 motif in place of one of its blades. This unexpected feature shows how a propeller structure can be assembled from subdomains with distinct folds. The HELP motif is not an independent domain but forms part of the hydrophobic core that joins the two beta-propellers. The TAPE domain binds alpha/beta-tubulin via its conserved, concave surface, including part of the atypical blade. Mapping the characteristic breakpoints of each EML4-ALK variant onto our structure indicates that the EML4 TAPE domain is truncated in many variants in a manner likely to make the fusion protein structurally unstable. We found that the heat shock protein 90 (Hsp90) inhibitor ganetespib induced degradation of these variants whereas others lacking a partial TAPE domain were resistant in both overexpression models and patient-derived cell lines. The Hsp90-sensitive EML4-ALK variants are exceptions to the rule that oncogenic fusion proteins involve breakpoints in disordered regions of both partners.


==About this Structure==
Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical beta-propeller domain.,Richards MW, Law EW, Rennalls LP, Busacca S, O'Regan L, Fry AM, Fennell DA, Bayliss R Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5195-200. doi:, 10.1073/pnas.1322892111. Epub 2014 Mar 24. PMID:24706829<ref>PMID:24706829</ref>
[[4ci8]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CI8 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
<ref group="xtra">PMID:024706829</ref><references group="xtra"/><references/>
</div>
[[Category: Bayliss, R.]]
<div class="pdbe-citations 4ci8" style="background-color:#fffaf0;"></div>
[[Category: Richards, M W.]]
== References ==
[[Category: Beta propeller]]
<references/>
[[Category: Eml1]]
__TOC__
[[Category: Eml4-alk]]
</StructureSection>
[[Category: Hsp90 inhibitor]]
[[Category: Homo sapiens]]
[[Category: Structural protein]]
[[Category: Large Structures]]
[[Category: Tubulin-binding]]
[[Category: Bayliss R]]
[[Category: Richards MW]]
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