8bbe

From Proteopedia

(Difference between revisions)

Current revision

Structure of the IFT-A complex; IFT-A2 module

Structural highlights

8bbe is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IF122_HUMAN Cranioectodermal dysplasia;Short rib-polydactyly syndrome, Beemer-Langer type. The disease is caused by variants affecting the gene represented in this entry.

Function

IF122_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 required in ciliogenesis and ciliary protein trafficking (PubMed:27932497, PubMed:29220510). Involved in cilia formation during neuronal patterning. Acts as a negative regulator of Shh signaling. Required to recruit TULP3 to primary cilia (By similarity).[UniProtKB:Q6NWV3]^[1] ^[2]

Publication Abstract from PubMed

Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes, interacts with IFT-B, and uses an array of beta-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-AâTULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK-the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A's distinct functions, provide a blueprint for IFT-A in the train, and shed light on how IFT evolved from a proto-coatomer ancestor.

IFT-A structure reveals carriages for membrane protein transport into cilia.,Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova K, Roberts AJ Cell. 2022 Dec 22;185(26):4971-4985.e16. doi: 10.1016/j.cell.2022.11.010. Epub , 2022 Dec 2. PMID:36462505^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hirano T, Katoh Y, Nakayama K. Intraflagellar transport-A complex mediates ciliary entry and retrograde trafficking of ciliary G protein-coupled receptors. Mol Biol Cell. 2017 Feb 1;28(3):429-439. PMID:27932497 doi:10.1091/mbc.E16-11-0813
↑ Takahara M, Katoh Y, Nakamura K, Hirano T, Sugawa M, Tsurumi Y, Nakayama K. Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but not ciliogenesis. Hum Mol Genet. 2018 Feb 1;27(3):516-528. PMID:29220510 doi:10.1093/hmg/ddx421
↑ Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova K, Roberts AJ. IFT-A structure reveals carriages for membrane protein transport into cilia. Cell. 2022 Nov 30:S0092-8674(22)01422-2. doi: 10.1016/j.cell.2022.11.010. PMID:36462505 doi:http://dx.doi.org/10.1016/j.cell.2022.11.010

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8bbe"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8bbe is ON HOLD
+==Structure of the IFT-A complex; IFT-A2 module==
+<StructureSection load='8bbe' size='340' side='right'caption='[[8bbe]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8bbe]] is a 4 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=8BBE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BBE 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]] 3.5&#8491;</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=8bbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bbe OCA], [https://pdbe.org/8bbe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bbe RCSB], [https://www.ebi.ac.uk/pdbsum/8bbe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bbe ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/IF122_HUMAN IF122_HUMAN] Cranioectodermal dysplasia;Short rib-polydactyly syndrome, Beemer-Langer type. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/IF122_HUMAN IF122_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 required in ciliogenesis and ciliary protein trafficking (PubMed:27932497, PubMed:29220510). Involved in cilia formation during neuronal patterning. Acts as a negative regulator of Shh signaling. Required to recruit TULP3 to primary cilia (By similarity).[UniProtKB:Q6NWV3]<ref>PMID:27932497</ref> <ref>PMID:29220510</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Intraflagellar transport (IFT) trains are massive molecular machines that traffic proteins between cilia and the cell body. Each IFT train is a dynamic polymer of two large complexes (IFT-A and -B) and motor proteins, posing a formidable challenge to mechanistic understanding. Here, we reconstituted the complete human IFT-A complex and obtained its structure using cryo-EM. Combined with AlphaFold prediction and genome-editing studies, our results illuminate how IFT-A polymerizes, interacts with IFT-B, and uses an array of beta-propeller and TPR domains to create "carriages" of the IFT train that engage TULP adaptor proteins. We show that IFT-AâTULP carriages are essential for cilia localization of diverse membrane proteins, as well as ICK-the key kinase regulating IFT train turnaround. These data establish a structural link between IFT-A's distinct functions, provide a blueprint for IFT-A in the train, and shed light on how IFT evolved from a proto-coatomer ancestor.
-Authors:
+IFT-A structure reveals carriages for membrane protein transport into cilia.,Hesketh SJ, Mukhopadhyay AG, Nakamura D, Toropova K, Roberts AJ Cell. 2022 Dec 22;185(26):4971-4985.e16. doi: 10.1016/j.cell.2022.11.010. Epub , 2022 Dec 2. PMID:36462505<ref>PMID:36462505</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8bbe" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Hesketh SJ]]
+[[Category: Mukhopadhyay AG]]
+[[Category: Nakamura D]]
+[[Category: Roberts AJ]]
+[[Category: Toropova K]]

8bbe

From Proteopedia

Current revision

Structure of the IFT-A complex; IFT-A2 module

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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