View source for 8fh3


==Human IFT-A complex structures provide molecular insights into ciliary transport==
<StructureSection load='8fh3' size='340' side='right'caption='[[8fh3]], [[Resolution|resolution]] 4.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fh3]] is a 5 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=8FH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FH3 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]] 4.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=8fh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fh3 OCA], [https://pdbe.org/8fh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fh3 RCSB], [https://www.ebi.ac.uk/pdbsum/8fh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fh3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/WDR35_HUMAN WDR35_HUMAN] Cranioectodermal dysplasia;Short rib-polydactyly syndrome type 5;Short rib-polydactyly syndrome, Verma-Naumoff type. The disease is caused by variants affecting the gene represented in this entry.  The disease is caused by variants affecting the gene represented in this entry. WDR35 mutations cause short rib-polydactyly syndrome through impaired cilia formation. Primary fibroblasts from SRTD7 patients lacking WDR35 fail to produce cilia (PubMed:21473986).<ref>PMID:21473986</ref>   The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. SRTD7/20 can be caused by co-occurrence of WDR35 variant p.Trp311Leu and INTU p.Gln276Ter. One such patient has been reported.<ref>PMID:27158779</ref> 
== Function ==
[https://www.uniprot.org/uniprot/WDR35_HUMAN WDR35_HUMAN] As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis and ciliary protein trafficking (PubMed:21473986, PubMed:28400947, PubMed:29220510). May promote CASP3 activation and TNF-stimulated apoptosis.<ref>PMID:20193664</ref> <ref>PMID:21473986</ref> <ref>PMID:28400947</ref> <ref>PMID:29220510</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Intraflagellar transport (IFT) complexes, IFT-A and IFT-B, form bidirectional trains that move along the axonemal microtubules and are essential for assembling and maintaining cilia. Mutations in IFT subunits lead to numerous ciliopathies involving multiple tissues. However, how IFT complexes assemble and mediate cargo transport lacks mechanistic understanding due to missing high-resolution structural information of the holo-complexes. Here we report cryo-EM structures of human IFT-A complexes in the presence and absence of TULP3 at overall resolutions of 3.0-3.9 A. IFT-A adopts a "lariat" shape with interconnected core and peripheral subunits linked by structurally vital zinc-binding domains. TULP3, the cargo adapter, interacts with IFT-A through its N-terminal region, and interface mutations disrupt cargo transport. We also determine the molecular impacts of disease mutations on complex formation and ciliary transport. Our work reveals IFT-A architecture, sheds light on ciliary transport and IFT train formation, and enables the rationalization of disease mutations in ciliopathies.

Human IFT-A complex structures provide molecular insights into ciliary transport.,Jiang M, Palicharla VR, Miller D, Hwang SH, Zhu H, Hixson P, Mukhopadhyay S, Sun J Cell Res. 2023 Apr;33(4):288-298. doi: 10.1038/s41422-023-00778-3. Epub 2023 Feb , 13. PMID:36775821<ref>PMID:36775821</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fh3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Hixson P]]
[[Category: Hwang SH]]
[[Category: Jiang M]]
[[Category: Miller D]]
[[Category: Mukhopadhyay S]]
[[Category: Palicharla VR]]
[[Category: Sun J]]
[[Category: Zhu H]]