Open Access Release: ‘Allosteric network of dynamic coupling within BAP1-UCH revealed by methyl NMR’ in Nature Communications
A team led by WPI-SKCM² Co-PI Chin-Hsuan Lai and PI Shang-Te Danny Hsu has made their Nature Communications paper, “Allosteric network of dynamic coupling within BAP1-UCH revealed by methyl NMR,” newly available as open access.
The team introduced 22 cancer mutations and additional methyl mutations on the other 22 cancer mutation sites of BAP1-UCH to map their effects on the methyl chemical shifts. Their analysis reveals an allosteric coupling network centered on a conserved leucine (L49) shared across human UCH paralogs.
Remarkably, a single-carbon side-chain truncation in the L49V variant abolishes DUB activity, coinciding with disruption of correlated μs–ms timescale motions within a phenylalanine cluster that undergoes converted motions within the L49 hub.
Their findings revealed how BAP1-UCH sustains its catalytic competence through a delicately tuned dynamic network and how minute alterations can collapse this allosteric balance, providing mechanistic link between subtle structural perturbations and oncogenesis.
In their paper, the authors concluded that their study provides compelling evidence that the functional integrity of BAP1-UCH is governed by a delicate network of allosteric interactions, underpinned by an intricate web of side chain dynamics and conserved aromatic residues.
By uncovering how subtle structural perturbations influence correlated molecular motions and protein function, this work contributes to ongoing research at WPI-SKCM² aimed at understanding topological and chiral phenomena across scales and systems.
Paper Information
Journal: Nature Communications (2026)
Title: Allosteric network of dynamic coupling within BAP1-UCH revealed by methyl NMR
Authors: Chih-Hsuan Lai, Yuan-Chao Lou, Chi-Fon Chang, Wei-Lin Lu, Manoj Kumar Sriramoju, Yong-Sheng Wang,Kuen-Phon Wu, Carlo Camilloni & Shang-Te Danny Hsu
