View source for 1uuj


==N-terminal domain of Lissencephaly-1 protein (Lis-1)==
<StructureSection load='1uuj' size='340' side='right'caption='[[1uuj]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uuj]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UUJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UUJ 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]] 1.75&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <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=1uuj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uuj OCA], [https://pdbe.org/1uuj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uuj RCSB], [https://www.ebi.ac.uk/pdbsum/1uuj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uuj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LIS1_MOUSE LIS1_MOUSE] Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. Required during brain development for the proliferation of neuronal precursors and the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Neuronal migration involves a process called nucleokinesis, whereby migrating cells extend an anterior process into which the nucleus subsequently translocates. During nucleokinesis dynein at the nuclear surface may translocate the nucleus towards the centrosome by exerting force on centrosomal microtubules. Also required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. May also play a role in other forms of cell locomotion including the migration of fibroblasts during wound healing. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position. Required for dynein recruitment to microtubule plus ends and BICD2-bound cargos (By similarity). May modulate the Reelin pathway through interaction of the PAF-AH (I) catalytic dimer with VLDLR (PubMed:17330141).[UniProtKB:P43033][UniProtKB:P43034][HAMAP-Rule:MF_03141]<ref>PMID:11056530</ref> <ref>PMID:11344260</ref> <ref>PMID:12796778</ref> <ref>PMID:12911752</ref> <ref>PMID:14507966</ref> <ref>PMID:14578885</ref> <ref>PMID:14691133</ref> <ref>PMID:15173193</ref> <ref>PMID:15473966</ref> <ref>PMID:16107726</ref> <ref>PMID:16203747</ref> <ref>PMID:16369480</ref> <ref>PMID:16481446</ref> <ref>PMID:17330141</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uu/1uuj_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1uuj ConSurf].
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== Publication Abstract from PubMed ==
Mutations in the Lis1 gene result in lissencephaly (smooth brain), a debilitating developmental syndrome caused by the impaired ability of postmitotic neurons to migrate to their correct destination in the cerebral cortex. Sequence similarities suggest that the LIS1 protein contains a C-terminal seven-blade beta-propeller domain, while the structure of the N-terminal fragment includes the LisH (Lis-homology) motif, a pattern found in over 100 eukaryotic proteins with a hitherto unknown function. We present the 1.75 A resolution crystal structure of the N-terminal domain of mouse LIS1, and we show that the LisH motif is a novel, thermodynamically very stable dimerization domain. The structure explains the molecular basis of a low severity form of lissencephaly.

The structure of the N-terminal domain of the product of the lissencephaly gene Lis1 and its functional implications.,Kim MH, Cooper DR, Oleksy A, Devedjiev Y, Derewenda U, Reiner O, Otlewski J, Derewenda ZS Structure. 2004 Jun;12(6):987-98. PMID:15274919<ref>PMID:15274919</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1uuj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phospholipase A2 3D structures|Phospholipase A2 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cooper DR]]
[[Category: Derewenda U]]
[[Category: Derewenda ZS]]
[[Category: Devedjiev Y]]
[[Category: Kim MH]]