Journal Article

FZJ-2020-02595

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Role of Tyr-39 for the Structural Features of α-Synuclein and for the Interaction with a Strong Modulator of Its Amyloid Assembly

Palomino, O.FZJ* ; Buratti, F. A. ; Sacco, P. S. ; Rossetti, G.FZJ* ; Carloni, P. (Corresponding author)FZJ* ; Fernandez, C. O. (Corresponding author)

2020
Molecular Diversity Preservation International Basel

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/25441  doi:10.3390/ijms21145061

Abstract: Recent studies suggest that Tyr-39 might play a critical role for both the normal function and the pathological dysfunction of α-synuclein (αS), an intrinsically disordered protein involved in Parkinson’s disease. We perform here a comparative analysis between the structural features of human αS and its Y39A, Y39F, and Y39L variants. By the combined application of site-directed mutagenesis, biophysical techniques, and enhanced sampling molecular simulations, we show that removing aromatic functionality at position 39 of monomeric αS leads to protein variants populating more compact conformations, conserving its disordered nature and secondary structure propensities. Contrasting with the subtle changes induced by mutations on the protein structure, removing aromaticity at position 39 impacts strongly on the interaction of αS with the potent amyloid inhibitor phthalocyanine tetrasulfonate (PcTS). Our findings further support the role of Tyr-39 in forming essential inter and intramolecular contacts that might have important repercussions for the function and the dysfunction of αS.

---

Contributing Institute(s):

1. Jara-Institut Quantum Information (INM-11)
2. Jülich Supercomputing Center (JSC)
3. Computational Biomedicine (INM-9)
4. Computational Biomedicine (IAS-5)
5. JARA - HPC (JARA-HPC)

Research Program(s):

1. 511 - Computational Science and Mathematical Methods (POF3-511) (POF3-511)
2. Exploring the conformational properties of alpha-synuclein variants: an enhanced sampling study (jara0209_20200501) (jara0209_20200501)

Appears in the scientific report 2020

---

Database coverage:
; ; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---