View source for 8dyu


==Structure of human cytoplasmic dynein-1 bound to two Lis1 proteins==
<StructureSection load='8dyu' size='340' side='right'caption='[[8dyu]], [[Resolution|resolution]] 4.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8dyu]] is a 3 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=8DYU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DYU 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]] 4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</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=8dyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dyu OCA], [https://pdbe.org/8dyu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dyu RCSB], [https://www.ebi.ac.uk/pdbsum/8dyu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dyu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DYHC1_HUMAN DYHC1_HUMAN] Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures;Autosomal dominant non-syndromic intellectual disability;Autosomal dominant Charcot-Marie-Tooth disease type 2O. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/DYHC1_HUMAN DYHC1_HUMAN] Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Plays a role in mitotic spindle assembly and metaphase plate congression (PubMed:27462074).<ref>PMID:27462074</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The lissencephaly 1 protein, LIS1, is mutated in type-1 lissencephaly and is a key regulator of cytoplasmic dynein-1. At a molecular level, current models propose that LIS1 activates dynein by relieving its autoinhibited form. Previously we reported a 3.1 A structure of yeast dynein bound to Pac1, the yeast homologue of LIS1, which revealed the details of their interactions (Gillies et al., 2022). Based on this structure, we made mutations that disrupted these interactions and showed that they were required for dynein's function in vivo in yeast. We also used our yeast dynein-Pac1 structure to design mutations in human dynein to probe the role of LIS1 in promoting the assembly of active dynein complexes. These mutations had relatively mild effects on dynein activation, suggesting that there may be differences in how dynein and Pac1/LIS1 interact between yeast and humans. Here, we report cryo-EM structures of human dynein-LIS1 complexes. Our new structures reveal the differences between the yeast and human systems, provide a blueprint to disrupt the human dynein-LIS1 interactions more accurately, and map type-1 lissencephaly disease mutations, as well as mutations in dynein linked to malformations of cortical development/intellectual disability, in the context of the dynein-LIS1 complex.

Structures of human dynein in complex with the lissencephaly 1 protein, LIS1.,Reimer JM, DeSantis ME, Reck-Peterson SL, Leschziner AE Elife. 2023 Jan 24;12:e84302. doi: 10.7554/eLife.84302. PMID:36692009<ref>PMID:36692009</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8dyu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dynein 3D structures|Dynein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: DeSantis M]]
[[Category: Leschziner AE]]
[[Category: Reck-Peterson SL]]
[[Category: Reimer JM]]