RT info:eu-repo/semantics/article
T1 PSTPIP1-LYP phosphatase interaction: structural basis and implications for autoinflammatory disorders
A1 Manso, José A.
A1 Marcos, Tamara
A1 Ruiz-Martín, Virginia
A1 Casas Requena, Javier
A1 Alcón, Pablo
A1 Sánchez Crespo, Mariano
A1 Bayón Prieto, Yolanda
A1 de Pereda, José M.
A1 Alonso, Andrés
AB Mutations in the adaptor protein PSTPIP1 cause a spectrum of autoinflammatory diseases, including PAPA and PAMI; however, the mechanism underlying these diseases remains unknown. Most of these mutations lie in PSTPIP1 F-BAR domain, which binds to LYP, a protein tyrosine phosphatase associated with arthritis and lupus. To shed light on the mechanism by which these mutations generate autoinflammatory disorders, we solved the structure of the F-BAR domain of PSTPIP1 alone and bound to the C-terminal homology segment of LYP, revealing a novel mechanism of recognition of Pro-rich motifs by proteins in which a single LYP molecule binds to the PSTPIP1 F-BAR dimer. The residues R228, D246, E250, and E257 of PSTPIP1 that are mutated in immunological diseases directly interact with LYP. These findings link the disruption of the PSTPIP1/LYP interaction to these diseases, and support a critical role for LYP phosphatase in their pathogenesis.
SN 1420-682X
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/64306
UL https://uvadoc.uva.es/handle/10324/64306
LA eng
NO Cell Mol Life Sci 79:131. https://doi.org/10.1007/s00018-022-04173-w
NO Producción Científica
DS UVaDOC
RD 05-ene-2025