PXD037049

PXD037049 is an original dataset announced via ProteomeXchange.

Title	Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B
Description	Cilia are ubiquitous eukaryotic organelles impotant for cellular motility, signaling, and sensory reception. Cilium formation requires intraflagellar transport of structural and signaling components and involves 22 different proteins organized into intraflagellar transport (IFT) complexes IFT-A and IFT-B that are transported by molecular motors. The IFT-B complex constitutes the backbone of polymeric IFT trains carrying cargo between the cilium and the cell body. Currently, high-resolution structures are only available for smaller IFT-B subcomplexes leaving > 50% structurally uncharacterized. Here, we used Alphafold to structurally model the 15-subunit IFT-B complex. The model was validated using cross-linking/mass-spectrometry data on reconstituted IFT-B complexes, X-ray scattering in solution, diffraction from crystals as well as site-directed mutagenesis and protein-binding assays. The IFT-B structure reveals an elongated and highly flexible complex consistent with cryo-electron tomographic reconstructions of IFT trains. The IFT-B complex organizes into IFT-B1 and IFT-B2 parts with binding sites for ciliary cargo and the inactive IFT dynein motor, respectively. Interestingly, our results are consistent with two different binding sites for IFT81/74 on IFT88/70/52/46 suggesting the possibility of different structural architectures for the IFT-B1 complex. Our data present a structural framework to understand IFT-B complex assembly, function, and ciliopathy variants.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:55:34.176.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jens Andersen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-27 11:40:46	ID requested
1	2022-12-02 02:05:22	announced
⏵ 2	2023-11-14 07:55:35	announced	2023-11-14: Updated project metadata.

Petriman NA, Loureiro-L, ó, pez M, Taschner M, Zacharia NK, Georgieva MM, Boegholm N, Wang J, Mour, ã, o A, Russell RB, Andersen JS, Lorentzen E, Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B. EMBO J, 41(24):e112440(2022) [pubmed]

submitter keyword: Protein structure, Intraflagellar Transport, Cross-linking, Proteomics,Cilia

Jens S. Andersen
contact affiliation	University of Southern Denmark, Department of Biochemistry and Molecular Biology, Campusvej 55, DK-5230 Odense M, Denmark
contact email	jens.andersen@bmb.sdu.dk
lab head
Jens Andersen
contact affiliation	University of Southern Denmark, Department og Biochemistry and Molecular Biology
contact email	jens.andersen@bmb.sdu.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037049
     1. Label: PRIDE project
     2. Name: Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B