View source for 6sc2


==Structure of the dynein-2 complex; IFT-train bound model==
<SX load='6sc2' size='340' side='right' viewer='molstar' caption='[[6sc2]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6sc2]] is a 14 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=6SC2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SC2 FirstGlance]. <br>
</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>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WDR60 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), WDR34 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DYNC2LI1, D2LIC, LIC3, CGI-60 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DYNLRB1, BITH, DNCL2A, DNLC2A, ROBLD1, HSPC162 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), DYNLL1, DLC1, DNCL1, DNCLC1, HDLC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sc2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sc2 OCA], [http://pdbe.org/6sc2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sc2 RCSB], [http://www.ebi.ac.uk/pdbsum/6sc2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sc2 ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/WDR60_HUMAN WDR60_HUMAN]] Short rib-polydactyly syndrome, Verma-Naumoff type;Jeune syndrome. The disease is caused by mutations affecting the gene represented in this entry. Fibroblasts from affected individuals exhibit a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. [[http://www.uniprot.org/uniprot/WDR34_HUMAN WDR34_HUMAN]] Short rib-polydactyly syndrome, Verma-Naumoff type;Jeune syndrome. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/DC2L1_HUMAN DC2L1_HUMAN]] Jeune syndrome;Ellis Van Creveld syndrome. The disease is caused by mutations affecting the gene represented in this entry. 
== Function ==
[[http://www.uniprot.org/uniprot/DLRB1_HUMAN DLRB1_HUMAN]] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. [[http://www.uniprot.org/uniprot/WDR60_HUMAN WDR60_HUMAN]] May play a role in ciliogenesis.<ref>PMID:23910462</ref>  [[http://www.uniprot.org/uniprot/DYL1_HUMAN DYL1_HUMAN]] Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Binds and inhibits the catalytic activity of neuronal nitric oxide synthase.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>   Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.<ref>PMID:10198631</ref> <ref>PMID:15193260</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref>  [[http://www.uniprot.org/uniprot/WDR34_HUMAN WDR34_HUMAN]] Critical for ciliary functions, essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-motor-based intraflagellar transport (IFT) machinery. Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Inhibits the MAP3K7-induced NF-kappa-B activation pathway. Inhibits MAP3K7 phosphorylation at 'Thr-184' and 'Thr-187' upon Il-1 beta stimulation.<ref>PMID:19521662</ref> <ref>PMID:24183449</ref>  [[http://www.uniprot.org/uniprot/DC2L1_HUMAN DC2L1_HUMAN]] Required for correct intraflagellar transport (IFT), the bi-directional movement of particles required for the assembly, maintenance and functioning of primary cilia. Involved in the regulation of ciliary length.<ref>PMID:26077881</ref> <ref>PMID:26130459</ref>  
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== Publication Abstract from PubMed ==
Dynein-2 assembles with polymeric intraflagellar transport (IFT) trains to form a transport machinery that is crucial for cilia biogenesis and signaling. Here we recombinantly expressed the ~1.4-MDa human dynein-2 complex and solved its cryo-EM structure to near-atomic resolution. The two identical copies of the dynein-2 heavy chain are contorted into different conformations by a WDR60-WDR34 heterodimer and a block of two RB and six LC8 light chains. One heavy chain is steered into a zig-zag conformation, which matches the periodicity of the anterograde IFT-B train. Contacts between adjacent dyneins along the train indicate a cooperative mode of assembly. Removal of the WDR60-WDR34-light chain subcomplex renders dynein-2 monomeric and relieves autoinhibition of its motility. Our results converge on a model in which an unusual stoichiometry of non-motor subunits controls dynein-2 assembly, asymmetry, and activity, giving mechanistic insight into the interaction of dynein-2 with IFT trains and the origin of diverse functions in the dynein family.

Structure of the dynein-2 complex and its assembly with intraflagellar transport trains.,Toropova K, Zalyte R, Mukhopadhyay AG, Mladenov M, Carter AP, Roberts AJ Nat Struct Mol Biol. 2019 Sep;26(9):823-829. doi: 10.1038/s41594-019-0286-y. Epub, 2019 Aug 26. PMID:31451806<ref>PMID:31451806</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 6sc2" style="background-color:#fffaf0;"></div>

==See Also==
*[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Carter, A P]]
[[Category: Mladenov, M]]
[[Category: Mukhopadhyay, A G]]
[[Category: Roberts, A J]]
[[Category: Toropova, K]]
[[Category: Zalyte, R]]
[[Category: Cilia]]
[[Category: Complex]]
[[Category: Dynein]]
[[Category: Intraflagellar transport]]
[[Category: Motor protein]]