8bbe
From Proteopedia
Structure of the IFT-A complex; IFT-A2 module
Structural highlights
DiseaseIFT43_HUMAN Cranioectodermal dysplasia. 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. The disease is caused by variants affecting the gene represented in this entry. FunctionIFT43_HUMAN As a component of 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 (PubMed:28400947, PubMed:28973684). Involved in retrograde ciliary transport along microtubules from the ciliary tip to the base (PubMed:21378380).[1] [2] [3] 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 Nov 30:S0092-8674(22)01422-2. doi: 10.1016/j.cell.2022.11.010. PMID:36462505[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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