8bbe
From Proteopedia
Structure of the IFT-A complex; IFT-A2 module
Structural highlights
DiseaseIF122_HUMAN Cranioectodermal dysplasia;Short rib-polydactyly syndrome, Beemer-Langer type. The disease is caused by variants affecting the gene represented in this entry. FunctionIF122_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 PubMedIntraflagellar 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-Aâ TULP 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
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