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4ci8
From Proteopedia
(Difference between revisions)
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| - | + | ==Crystal structure of the tandem atypical beta-propeller domain of EML1== | |
| - | + | <StructureSection load='4ci8' size='340' side='right' caption='[[4ci8]], [[Resolution|resolution]] 2.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[4ci8]] is a 2 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=4CI8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CI8 FirstGlance]. <br> | |
| - | ==Function== | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ci8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ci8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ci8 RCSB], [http://www.ebi.ac.uk/pdbsum/4ci8 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
[[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). | [[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). | ||
| + | <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. | ||
| - | + | 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> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| - | [[Category: Bayliss, R | + | == References == |
| - | [[Category: Richards, M W | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Bayliss, R]] | ||
| + | [[Category: Richards, M W]] | ||
[[Category: Beta propeller]] | [[Category: Beta propeller]] | ||
[[Category: Eml1]] | [[Category: Eml1]] | ||
Revision as of 14:02, 24 December 2014
Crystal structure of the tandem atypical beta-propeller domain of EML1
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