3dvt: Difference between revisions
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==Biochemical and structural characterization of the PAK1- LC8 interaction== | ==Biochemical and structural characterization of the PAK1- LC8 interaction== | ||
<StructureSection load='3dvt' size='340' side='right' caption='[[3dvt]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='3dvt' size='340' side='right'caption='[[3dvt]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3dvt]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3dvt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DVT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DVT FirstGlance]. <br> | ||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dvh|3dvh]], [[3dvp|3dvp]]</td></tr> | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3dvh|3dvh]], [[3dvp|3dvp]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ctp, Cdlc1, ddlc1, CG6998 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ctp, Cdlc1, ddlc1, CG6998 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3dvt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dvt OCA], [https://pdbe.org/3dvt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dvt RCSB], [https://www.ebi.ac.uk/pdbsum/3dvt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dvt ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/DYL1_DROME DYL1_DROME]] Acts as a non-catalytic accessory component of a dynein complex (By similarity). | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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==See Also== | ==See Also== | ||
*[[Dynein|Dynein]] | *[[Dynein 3D structures|Dynein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Drome]] | [[Category: Drome]] | ||
[[Category: Large Structures]] | |||
[[Category: LIghtcap, C M]] | [[Category: LIghtcap, C M]] | ||
[[Category: Williams, J C]] | [[Category: Williams, J C]] | ||
Revision as of 11:09, 9 February 2022
Biochemical and structural characterization of the PAK1- LC8 interactionBiochemical and structural characterization of the PAK1- LC8 interaction
Structural highlights
Function[DYL1_DROME] Acts as a non-catalytic accessory component of a dynein complex (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPak1 (p21-activated kinase-1) and the dynein light chain, LC8, are overexpressed in breast cancer, and their direct interaction has been proposed to regulate tumor cell survival. These effects have been attributed in part to Pak1-mediated phosphorylation of LC8 at serine 88. However, LC8 is homodimeric, which renders Ser(88) inaccessible. Moreover, Pak1 does not contain a canonical LC8 binding sequence compared with other characterized LC8 binding sequences. Together, these observations raise the question whether the Pak1/LC8 interaction is distinct (i.e. enabled by a unique interface independent of LC8 dimerization). Herein, we present results from biochemical, NMR, and crystallographic studies that show that Pak1 (residues 212-222) binds to LC8 along the same groove as canonical LC8 interaction partners (e.g. nNOS and BimL). Using LC8 point mutants K36P and T67A, we were able to differentiate Pak1 from canonical LC8 binding sequences and identify a key hydrogen bond network that compensates for the loss of the conserved glutamine in the consensus sequence. We also show that the target binding interface formed through LC8 dimerization is required to bind to Pak1 and precludes phosphorylation of LC8 at Ser(88). Consistent with this observation, in vitro phosphorylation assays using activated Pak1 fail to phosphorylate LC8. Although these results define structural details of the Pak1/LC8 interaction and suggest a hierarchy of target binding affinities, they do not support the current model whereby Pak1 binds to and subsequently phosphorylates LC8 to promote anchorage-independent growth. Rather, they suggest that LC8 binding modulates Pak1 activity and/or nuclear localization. Biochemical and structural characterization of the Pak1-LC8 interaction.,Lightcap CM, Sun S, Lear JD, Rodeck U, Polenova T, Williams JC J Biol Chem. 2008 Oct 3;283(40):27314-24. Epub 2008 Jul 23. PMID:18650427[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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