PXD059518

PXD059518 is an original dataset announced via ProteomeXchange.

Title	Structural Insights into the Role of the Proline Rich Region in Tau Function
Description	Tau is a microtubule-associated protein that plays an important role in modulating axonal microtubules in neurons. Intracellular tau aggregates are found in a broad class of disorders, including Alzheimer’s disease, termed tauopathies. Tau is an intrinsically disordered protein, and its structural disorder appears to be critical to its microtubule-related functions. Tubulin binding sites are found in tau’s proline-rich region (PRR), microtubule binding repeats (MTBR: R1–R4), and pseudo-repeat, R′. While many post-translational modifications have been identified on tau, phosphorylation sites, which both regulate tubulin dimer and microtubule interactions and are correlated with disease, cluster with high frequency within the PRR. Here, we use fluorescence correlation spectroscopy and structural mass spectrometry techniques to characterize the impact of phosphomimic mutations in the PRR on tubulin dimer binding and probe the structure of the PRR-tubulin dimer complex. We find that phosphomimics cumulatively diminish tubulin dimer binding and slow microtubule polymerization. Additionally, we map two ~15 residue regions of the PRR as primary tubulin dimer binding sites and propose a model in which PRR enhances lateral interactions between tubulin dimers, complementing the longitudinal interactions observed for MTBR. Together these measurements provide insight into the previously overlooked relevance of tau’s PRR in functional interactions with tubulin.
HostingRepository	PRIDE
AnnounceDate	2025-01-31
AnnouncementXML	Submission_2025-01-31_05:37:10.204.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059518
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Elizabeth Rhoades
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-07 11:27:24	ID requested
⏵ 1	2025-01-31 05:37:11	announced

Acosta K, Brue CR, Holubovska P, Kim HJ, Mayne L, Murakami K, Rhoades E, Structural insights into the role of the proline rich region in tau function. Structure, 33(3):465-474.e8(2025) [pubmed]

10.1016/j.str.2024.12.017;

10.1101/2024.09.20.614010;

10.6019/PXD059518;

Acosta K, Brue CR, Kim HJ, Holubovska P, Mayne L, Murakami K, Rhoades E, Structural Insights into the Role of the Proline Rich Region in Tau Function. bioRxiv, ():(2024) [pubmed]

submitter keyword: post-translational modifications,Alzheimer's Disease, tubulin, Tau, phosphorylation, microtubules, aggregation

Elizabeth Rhoades
contact affiliation	Professor Dept. of Chemistry University of Pennsylvania
contact email	elizabeth.rhoades@sas.upenn.edu
lab head
Elizabeth Rhoades
contact affiliation	University of Pennsylvania
contact email	elizabeth.rhoades@sas.upenn.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD059518

PRIDE project URI

• PRIDE
  1. PXD059518
     1. Label: PRIDE project
     2. Name: Structural Insights into the Role of the Proline Rich Region in Tau Function