Dataset Information

Structural Insights into the Role of the Proline Rich Region in Tau Function

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Escherichia Coli

DISEASE(S): Alzheimer's Disease

SUBMITTER: Elizabeth Rhoades

LAB HEAD: Elizabeth Rhoades

PROVIDER: PXD059518 | Pride | 2025-01-31

REPOSITORIES: pride

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Dataset's files

Source:

			Action	DRS
	4P_PRR_TUB_30s_pH74.mzXML	Mzxml
	4P_PRR_TUB_30s_pH74.raw	Raw
	4P_PRR_allH_pH74.mzXML	Mzxml
	4P_PRR_allH_pH74.raw	Raw
	4P_PRR_only_30s_pH74.mzXML	Mzxml

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Structural insights into the role of the proline rich region in tau function.

Acosta Karen K Brue Christopher R CR Holubovska Polina P Kim Hee Jong HJ Mayne Leland L Murakami Kenji K Rhoades Elizabeth E

Structure (London, England : 1993) 20250110

Tau plays an important role in modulating axonal microtubules in neurons, while intracellular tau aggregates are found in many neurodegenerative disorders. Tubulin binding sites are found in tau's proline-rich region (PRR), microtubule binding repeats (MTBRs), and pseudo-repeat (R'). Tau phosphorylation sites, which cluster with high frequency within the PRR, regulate tubulin interactions and correlates with disease. Here, we use fluorescence correlation spectroscopy and structural mass spectrom ...[more]

PMID: 39826549

Publication: 1/2

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