TY - JOUR
T1 - Mechanisms of pathogenesis of missense mutations on the KDM6A-H3 interaction in type 2 Kabuki Syndrome
AU - Petrizzelli, Francesco
AU - Biagini, Tommaso
AU - Barbieri, Alessandro
AU - Parca, Luca
AU - Panzironi, Noemi
AU - Castellana, Stefano
AU - Caputo, Viviana
AU - Vescovi, Angelo Luigi
AU - Carella, Massimo
AU - Mazza, Tommaso
N1 - Funding Information:
We gratefully acknowledge NVIDIA Corporation , the Amber Team and the “5x1000” voluntary contribution for supporting this research.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020
Y1 - 2020
N2 - Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, and then causing a loss of function effect.
AB - Mutations in genes encoding for histone methylation proteins are associated with several developmental disorders. Among them, KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease. While nonsense mutations and short insertions/deletions are known to trigger pathogenic mechanisms, the functional effects of missense mutations are still uncharacterized. In this study, we demonstrate that a selected set of missense mutations significantly hamper the interaction between KDM6A and the histone H3, by modifying the dynamics of the linker domain, and then causing a loss of function effect.
KW - Computational biology
KW - Histone demethylation
KW - KDM6A
KW - Kabuki Syndrome
KW - Molecular dynamics simulation
UR - http://www.scopus.com/inward/record.url?scp=85089078634&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089078634&partnerID=8YFLogxK
U2 - 10.1016/j.csbj.2020.07.013
DO - 10.1016/j.csbj.2020.07.013
M3 - Article
AN - SCOPUS:85089078634
VL - 18
SP - 2033
EP - 2042
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
SN - 2001-0370
ER -