Reduced binding of Tau(210-240) to BIN1: Phosphate charges prefer n-Src/distal loops over RT-Src loops
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10505830" target="_blank" >RIV/00216208:11160/25:10505830 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/25:00143527
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.P51Hrel.Y" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=.P51Hrel.Y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bpj.2025.09.037" target="_blank" >10.1016/j.bpj.2025.09.037</a>
Alternative languages
Result language
angličtina
Original language name
Reduced binding of Tau(210-240) to BIN1: Phosphate charges prefer n-Src/distal loops over RT-Src loops
Original language description
Within the disordered tangles of Tau is a proline-rich region, which is selectively targeted by the SH3 domain of BIN1, a known genetic factor for Alzheimer disease, and may hold the key to understanding the disorder and treatment strategies. Hyperphosphorylation of Tau is known to disrupt complex formation, providing researchers with excellent preventative or remediative targets. This work compiles an extensive (>60 mu s) collection of all-atomistic molecular dynamics simulations of the Tau(210-240) fragment, representing the majority of the P2 subdomain of the proline-rich region, benchmarking various force fields, phosphorylations, and modifications against experimental NMR chemical shifts and spin-spin coupling for comparison. Additionally, several simulations of the binding complex were analyzed for their binding energies by MMGBSA calculations and computational alanine scanning to pinpoint the exact residues involved and the disruptions caused by the phosphate group. We noted that the additional charges decrease salt bridges formed by positive residues in Tau, particularly on R221, and negative residues in BIN1 by up to 32%, and a strong preference in Tau, particularly in the latter half, for contact toward the distal and n-Src loops instead of residues in the RT-Src loop.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10301 - Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect)
Result continuities
Project
—
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Biophysical Journal
ISSN
0006-3495
e-ISSN
1542-0086
Volume of the periodical
124
Issue of the periodical within the volume
21
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
3800-3810
UT code for WoS article
001616097400027
EID of the result in the Scopus database
2-s2.0-105020027602