6sc2
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==Structure of the dynein-2 complex; IFT-train bound model== |
| + | <SX load='6sc2' size='340' side='right' viewer='molstar' caption='[[6sc2]], [[Resolution|resolution]] 3.90Å' 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SC2 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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://oca.weizmann.ac.il/oca-docs/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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6sc2" style="background-color:#fffaf0;"></div> | ||
| + | == 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]] | ||
Revision as of 00:46, 7 March 2020
Structure of the dynein-2 complex; IFT-train bound model
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